rs8112524

chr19-2250529-G-Achr19-2250529-G-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0860

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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.602 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMH	NM_000479.5	c.555+50G>A		intron_variant		ENST00000221496.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMH	ENST00000221496.5	c.555+50G>A		intron_variant		1	NM_000479.5	P1
AMH	ENST00000589313.2	n.786G>A		non_coding_transcript_exon_variant	1/3	5
AMH	ENST00000592877.1	n.437-123G>A		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes AF: 0.517 AC: 78486 AN: 151900 Hom.: 21440 Cov.: 33

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

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.: 50 AF XY: 0.585 AC XY: 400179 AN XY: 684476

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.: 33 AF XY: 0.513 AC XY: 38159 AN XY: 74318

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:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

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

Other links and lift over

dbSNP: rs8112524; hg19: chr19-2250528; COSMIC: COSV55556302; COSMIC: COSV55556302;