rs11170553

Positions:

• chr12-53428308-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020547.3(AMHR2):​c.853-588C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0464 in 152,298 control chromosomes in the GnomAD database, including 214 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.046 (214 hom., cov: 32)
• Consequence: AMHR2 NM_020547.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900

Genes affected

AMHR2 (HGNC:465): (anti-Mullerian hormone receptor type 2) This gene encodes the receptor for the anti-Mullerian hormone (AMH) which, in addition to testosterone, results in male sex differentiation. AMH and testosterone are produced in the testes by different cells and have different effects. Testosterone promotes the development of male genitalia while the binding of AMH to the encoded receptor prevents the development of the mullerian ducts into uterus and Fallopian tubes. Mutations in this gene are associated with persistent Mullerian duct syndrome type II. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0739 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AMHR2	NM_020547.3	c.853-588C>T		intron_variant		ENST00000257863.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AMHR2	ENST00000257863.9	c.853-588C>T		intron_variant		1	NM_020547.3	P1

Frequencies

GnomAD3 genomes AF: 0.0464 AC: 7062 AN: 152180 Hom.: 214 Cov.: 32

Gnomad AFR AF: 0.0132

Gnomad AMI AF: 0.0186

Gnomad AMR AF: 0.0378

Gnomad ASJ AF: 0.0476

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0180

Gnomad FIN AF: 0.0395

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0756

Gnomad OTH AF: 0.0454

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0464 AC: 7061 AN: 152298 Hom.: 214 Cov.: 32 AF XY: 0.0438 AC XY: 3260 AN XY: 74466

Gnomad4 AFR AF: 0.0131

Gnomad4 AMR AF: 0.0377

Gnomad4 ASJ AF: 0.0476

Gnomad4 EAS AF: 0.000578

Gnomad4 SAS AF: 0.0180

Gnomad4 FIN AF: 0.0395

Gnomad4 NFE AF: 0.0756

Gnomad4 OTH AF: 0.0449

Alfa AF: 0.0529 Hom.: 28

Bravo AF: 0.0446

Asia WGS AF: 0.00837 AC: 29 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	6.8
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs11170553; hg19: chr12-53822092;