NM_030943.4:c.-74C>T

Variant names:

• chr14-102922615-C-T
• rs57687948
• NM_030943.4:c.-74C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_030943.4(AMN):​c.-74C>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. 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: AMN NM_030943.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.55
• Publications: 5 publications found

Genes affected

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]

AMN Gene-Disease associations (from GenCC):

• Imerslund-Grasbeck syndrome type 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• Imerslund-Grasbeck syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.-74C>T		upstream_gene_variant		ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.-255C>T		upstream_gene_variant			NP_001412175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	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

African (AFR) AF: 0.222 AC: 7062 AN: 31874

American (AMR) AF: 0.0768 AC: 2785 AN: 36282

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1291 AN: 24886

East Asian (EAS) AF: 0.00125 AC: 47 AN: 37584

South Asian (SAS) AF: 0.0816 AC: 6497 AN: 79576

European-Finnish (FIN) AF: 0.0674 AC: 2647 AN: 39288

Middle Eastern (MID) AF: 0.0833 AC: 446 AN: 5356

European-Non Finnish (NFE) AF: 0.0669 AC: 71671 AN: 1070716

Other (OTH) AF: 0.0725 AC: 4176 AN: 57634

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

African (AFR) AF: 0.216 AC: 8959 AN: 41474

American (AMR) AF: 0.0836 AC: 1278 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0467 AC: 162 AN: 3470

East Asian (EAS) AF: 0.00213 AC: 11 AN: 5170

South Asian (SAS) AF: 0.0811 AC: 391 AN: 4820

European-Finnish (FIN) AF: 0.0664 AC: 704 AN: 10602

Middle Eastern (MID) AF: 0.0748 AC: 22 AN: 294

European-Non Finnish (NFE) AF: 0.0691 AC: 4701 AN: 67998

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

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

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Oct 31, 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	-0.77
CADD	Benign	7.9
DANN	Benign	0.80
PhyloP100		1.5
PromoterAI		0.20	Neutral

Splicing

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

Other links and lift over

dbSNP: rs57687948; hg19: chr14-103388952;