rs8112524

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. Variant got -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

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 made for transcript

Verdict is Benign. Variant got -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AMH	NM_000479.5 link	c.555+50G>A	intron_variant	Intron 2 of 4	ENST00000221496.5	NP_000470.3	P03971
MIR4321	NR_036207.1 link	n.-110G>A	upstream_gene_variant
MIR4321	unassigned_transcript_3189	n.-159G>A	upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
AMH	ENST00000221496.5 link	c.555+50G>A	intron_variant	Intron 2 of 4	1	NM_000479.5	ENSP00000221496.2	P03971
AMH	ENST00000589313.2 link	n.786G>A	non_coding_transcript_exon_variant	Exon 1 of 3	5
AMH	ENST00000592877.1 link	n.437-123G>A	intron_variant	Intron 1 of 1	3
MIR4321	ENST00000592276.1 link	n.-110G>A	upstream_gene_variant		6

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

GnomAD3 exomes

AF:

0.534

AC:

77166

AN:

144390

Hom.:

21233

AF XY:

0.539

AC XY:

41834

AN XY:

77646

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 SAS exome

AF:

0.513

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

Gnomad4 AFR exome

AF:

0.339

Gnomad4 AMR exome

AF:

0.495

Gnomad4 ASJ exome

AF:

0.629

Gnomad4 EAS exome

AF:

0.421

Gnomad4 SAS exome

AF:

0.511

Gnomad4 FIN exome

AF:

0.531

Gnomad4 NFE exome

AF:

0.610

Gnomad4 OTH exome

AF:

0.570

GnomAD4 genome

AF:

0.516

AC:

78488

AN:

152018

Hom.:

21429

Cov.:

AF XY:

0.513

AC XY:

38159

AN XY:

74318

show subpopulations

Gnomad4 AFR

AF:

0.352

Gnomad4 AMR

AF:

0.555

Gnomad4 ASJ

AF:

0.638

Gnomad4 EAS

AF:

0.409

Gnomad4 SAS

AF:

0.502

Gnomad4 FIN

AF:

0.519

Gnomad4 NFE

AF:

0.606

Gnomad4 OTH

AF:

0.547

Alfa

AF:

0.597

Hom.:

24922

Bravo

AF:

0.510

Asia WGS

AF:

0.388

AC:

1353

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 10, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.73

CADD

Benign

5.9

DANN

Benign

0.90

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over