rs57687948

Positions:

• chr14-102922615-C-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.0737 in 1,535,338 control chromosomes in the GnomAD database, including 5,245 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1266 hom., cov: 32)
  • Exomes 𝑓: 0.070 (3979 hom.)
• Consequence: intergenic_region
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55

Genes affected

(HGNC:):

AMN (HGNC:14604): (amnion associated transmembrane protein) The protein encoded by this gene is a type I transmembrane protein. It is thought to modulate bone morphogenetic protein (BMP) receptor function by serving as an accessory or coreceptor, and thus facilitates or hinders BMP binding. It is known that the mouse AMN gene is expressed in the extraembryonic visceral endoderm layer during gastrulation, but it is found to be mutated in amnionless mouse. The encoded protein has sequence similarity to short gastrulation (Sog) and procollagen IIA proteins in Drosophila. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 14-102922615-C-T is Benign according to our data. Variant chr14-102922615-C-T is described in ClinVar as [Benign]. Clinvar id is 1243763.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.212 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.102922615C>T		intergenic_region
AMN	NM_030943.4	c.-74C>T		upstream_gene_variant		ENST00000299155.10	NP_112205.2
AMN	XM_011537202.4	c.-255C>T		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.-74C>T		upstream_gene_variant		1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16549 AN: 152024 Hom.: 1263 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.187

Gnomad AMR AF: 0.0831

Gnomad ASJ AF: 0.0467

Gnomad EAS AF: 0.00232

Gnomad SAS AF: 0.0817

Gnomad FIN AF: 0.0664

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.0691

Gnomad OTH AF: 0.0871

GnomAD4 exome AF: 0.0699 AC: 96622 AN: 1383196 Hom.: 3979 Cov.: 27 AF XY: 0.0698 AC XY: 47688 AN XY: 682998

Gnomad4 AFR exome AF: 0.222

Gnomad4 AMR exome AF: 0.0768

Gnomad4 ASJ exome AF: 0.0519

Gnomad4 EAS exome AF: 0.00125

Gnomad4 SAS exome AF: 0.0816

Gnomad4 FIN exome AF: 0.0674

Gnomad4 NFE exome AF: 0.0669

Gnomad4 OTH exome AF: 0.0725

GnomAD4 genome AF: 0.109 AC: 16580 AN: 152142 Hom.: 1266 Cov.: 32 AF XY: 0.108 AC XY: 8056 AN XY: 74382

Gnomad4 AFR AF: 0.216

Gnomad4 AMR AF: 0.0836

Gnomad4 ASJ AF: 0.0467

Gnomad4 EAS AF: 0.00213

Gnomad4 SAS AF: 0.0811

Gnomad4 FIN AF: 0.0664

Gnomad4 NFE AF: 0.0691

Gnomad4 OTH AF: 0.0862

Alfa AF: 0.101 Hom.: 178

Bravo AF: 0.116

Asia WGS AF: 0.0540 AC: 188 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Oct 31, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	7.9
DANN	Benign	0.80

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs57687948; hg19: chr14-103388952;