19-2250529-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000479.5(AMH):c.555+50G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.58 in 1,540,218 control chromosomes in the GnomAD database, including 263,320 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.52 ( 21429 hom., cov: 33)

Exomes 𝑓: 0.59 ( 241891 hom. )

Consequence

AMH
NM_000479.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.0860

Publications

11 publications found

Variant links:

Genes affected

AMH (HGNC:464): (anti-Mullerian hormone) This gene encodes a secreted ligand of the TGF-beta (transforming growth factor-beta) superfamily of proteins. Ligands of this family bind various TGF-beta receptors leading to recruitment and activation of SMAD family transcription factors that regulate gene expression. The encoded preproprotein is proteolytically processed to generate N- and C-terminal cleavage products that homodimerize and associate to form a biologically active noncovalent complex. This complex binds to the anti-Mullerian hormone receptor type 2 and causes the regression of Mullerian ducts in the male embryo that would otherwise differentiate into the uterus and fallopian tubes. This protein also plays a role in Leydig cell differentiation and function and follicular development in adult females. Mutations in this gene result in persistent Mullerian duct syndrome. [provided by RefSeq, Jul 2016]

AMH links:

MIR4321 (HGNC:38244): (microRNA 4321) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR4321 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.73).

BP6

Variant 19-2250529-G-A is Benign according to our data. Variant chr19-2250529-G-A is described in ClinVar as Benign. ClinVar VariationId is 1262695.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000479.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMH	NM_000479.5	MANE Select	c.555+50G>A		intron	N/A	NP_000470.3	P03971
	MIR4321	NR_036207.1		n.-110G>A		upstream_gene	N/A

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
AMH	ENST00000221496.5	TSL:1 MANE Select	c.555+50G>A	intron	N/A	ENSP00000221496.2	P03971
AMH	ENST00000589313.2	TSL:5	n.786G>A	non_coding_transcript_exon	Exon 1 of 3
AMH	ENST00000592877.1	TSL:3	n.437-123G>A	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.517

AC:

78486

AN:

151900

Hom.:

21440

Cov.:

show subpopulations

Gnomad AFR

AF:

0.353

Gnomad AMI

AF:

0.701

Gnomad AMR

AF:

0.555

Gnomad ASJ

AF:

0.638

Gnomad EAS

AF:

0.409

Gnomad SAS

AF:

0.502

Gnomad FIN

AF:

0.519

Gnomad MID

AF:

0.608

Gnomad NFE

AF:

0.607

Gnomad OTH

AF:

0.551

GnomAD2 exomes

AF:

0.534

AC:

77166

AN:

144390

AF XY:

0.539

show subpopulations

Gnomad AFR exome

AF:

0.334

Gnomad AMR exome

AF:

0.480

Gnomad ASJ exome

AF:

0.623

Gnomad EAS exome

AF:

0.396

Gnomad FIN exome

AF:

0.526

Gnomad NFE exome

AF:

0.607

Gnomad OTH exome

AF:

0.583

GnomAD4 exome

AF:

0.587

AC:

814215

AN:

1388200

Hom.:

241891

Cov.:

AF XY:

0.585

AC XY:

400179

AN XY:

684476

show subpopulations

African (AFR)

AF:

0.339

AC:

10688

AN:

31492

American (AMR)

AF:

0.495

AC:

17663

AN:

35674

Ashkenazi Jewish (ASJ)

AF:

0.629

AC:

15811

AN:

25122

East Asian (EAS)

AF:

0.421

AC:

15020

AN:

35642

South Asian (SAS)

AF:

0.511

AC:

40451

AN:

79092

European-Finnish (FIN)

AF:

0.531

AC:

22527

AN:

42448

Middle Eastern (MID)

AF:

0.626

AC:

2590

AN:

4138

European-Non Finnish (NFE)

AF:

0.610

AC:

656605

AN:

1076962

Other (OTH)

AF:

0.570

AC:

32860

AN:

57630

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

20899

41799

62698

83598

104497

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17890

35780

53670

71560

89450

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.516

AC:

78488

AN:

152018

Hom.:

21429

Cov.:

AF XY:

0.513

AC XY:

38159

AN XY:

74318

show subpopulations

African (AFR)

AF:

0.352

AC:

14606

AN:

41462

American (AMR)

AF:

0.555

AC:

8478

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.638

AC:

2213

AN:

3470

East Asian (EAS)

AF:

0.409

AC:

2109

AN:

5158

South Asian (SAS)

AF:

0.502

AC:

2422

AN:

4820

European-Finnish (FIN)

AF:

0.519

AC:

5502

AN:

10596

Middle Eastern (MID)

AF:

0.605

AC:

178

AN:

294

European-Non Finnish (NFE)

AF:

0.606

AC:

41191

AN:

67920

Other (OTH)

AF:

0.547

AC:

1150

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

1862

3724

5587

7449

9311

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

692

1384

2076

2768

3460

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.577

Hom.:

34812

Bravo

AF:

0.510

Asia WGS

AF:

0.388

AC:

1353

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.9

(source)

DANN

Benign

0.90

PhyloP100

0.086

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over