chr14-102930718-G-C

Variant names:

• chr14-102930718-G-C
• rs1190233
• NM_030943.4:c.*38G>C

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.*38G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.675 in 1,545,532 control chromosomes in the GnomAD database, including 353,428 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.65 (32317 hom., cov: 35)
  • Exomes 𝑓: 0.68 (321111 hom.)
• Consequence: AMN NM_030943.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.447
• Publications: 11 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=-0.9).
• BP6: Variant 14-102930718-G-C is Benign according to our data. Variant chr14-102930718-G-C is described in ClinVar as Benign. ClinVar VariationId is 1245489.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.715 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.*38G>C		3_prime_UTR_variant	Exon 12 of 12	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.*38G>C		3_prime_UTR_variant	Exon 12 of 12		NP_001412175.1
AMN	XM_011537203.4	c.*38G>C		3_prime_UTR_variant	Exon 12 of 12		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.*38G>C		3_prime_UTR_variant	Exon 12 of 12	1	NM_030943.4	ENSP00000299155.6

Frequencies

GnomAD3 genomes AF: 0.648 AC: 98587 AN: 152072 Hom.: 32297 Cov.: 35

Gnomad AFR AF: 0.566

Gnomad AMI AF: 0.644

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.735

Gnomad FIN AF: 0.630

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.676

Gnomad OTH AF: 0.671

GnomAD2 exomes AF: 0.681 AC: 101731 AN: 149292 AF XY: 0.686

Gnomad AFR exome AF: 0.570

Gnomad AMR exome AF: 0.695

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.687

Gnomad FIN exome AF: 0.645

Gnomad NFE exome AF: 0.680

Gnomad OTH exome AF: 0.702

GnomAD4 exome AF: 0.678 AC: 944785 AN: 1393342 Hom.: 321111 Cov.: 31 AF XY: 0.680 AC XY: 467846 AN XY: 688328

African (AFR) AF: 0.564 AC: 17820 AN: 31614

American (AMR) AF: 0.698 AC: 25333 AN: 36274

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 15757 AN: 25142

East Asian (EAS) AF: 0.708 AC: 25531 AN: 36042

South Asian (SAS) AF: 0.739 AC: 58610 AN: 79320

European-Finnish (FIN) AF: 0.647 AC: 29460 AN: 45562

Middle Eastern (MID) AF: 0.728 AC: 3323 AN: 4562

European-Non Finnish (NFE) AF: 0.678 AC: 729962 AN: 1077050

Other (OTH) AF: 0.675 AC: 38989 AN: 57776

GnomAD4 genome AF: 0.648 AC: 98662 AN: 152190 Hom.: 32317 Cov.: 35 AF XY: 0.652 AC XY: 48538 AN XY: 74410

African (AFR) AF: 0.566 AC: 23517 AN: 41524

American (AMR) AF: 0.712 AC: 10881 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2216 AN: 3472

East Asian (EAS) AF: 0.700 AC: 3619 AN: 5172

South Asian (SAS) AF: 0.736 AC: 3553 AN: 4830

European-Finnish (FIN) AF: 0.630 AC: 6676 AN: 10594

Middle Eastern (MID) AF: 0.745 AC: 219 AN: 294

European-Non Finnish (NFE) AF: 0.676 AC: 45976 AN: 67992

Other (OTH) AF: 0.672 AC: 1420 AN: 2112

Alfa AF: 0.606 Hom.: 3544

Bravo AF: 0.649

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

- -

Jul 07, 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	-0.90
CADD	Benign	0.27
DANN	Benign	0.64
PhyloP100		-0.45
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1190233; hg19: chr14-103397055; COSMIC: COSV54487842; COSMIC: COSV54487842;