rs1211497

Variant names:

• chr14-102922443-A-T
• rs1211497
• NM_030943.4:c.-246A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-102922443-A-T
• chr14-102922443-A-C
• chr14-102922443-A-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_030943.4(AMN):​c.-246A>T variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 152,028 control chromosomes in the GnomAD database, including 18,699 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (18699 hom., cov: 31)
• Consequence: AMN NM_030943.4 upstream_gene
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.62
• Publications: 2 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 14-102922443-A-T is Benign according to our data. Variant chr14-102922443-A-T is described in ClinVar as Benign. ClinVar VariationId is 1231371.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.735 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_030943.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	NM_030943.4	MANE Select	c.-246A>T		upstream_gene	N/A	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-427A>T		upstream_gene	N/A	NP_001412175.1	B3KP64

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	ENST00000299155.10	TSL:1 MANE Select	c.-246A>T		upstream_gene	N/A	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.-246A>T		upstream_gene	N/A	ENSP00000543058.1

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69280 AN: 151910 Hom.: 18645 Cov.: 31

Gnomad AFR AF: 0.742

Gnomad AMI AF: 0.288

Gnomad AMR AF: 0.480

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.355

Gnomad FIN AF: 0.365

Gnomad MID AF: 0.253

Gnomad NFE AF: 0.298

Gnomad OTH AF: 0.440

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

GnomAD4 genome AF: 0.457 AC: 69402 AN: 152028 Hom.: 18699 Cov.: 31 AF XY: 0.457 AC XY: 33961 AN XY: 74328

African (AFR) AF: 0.742 AC: 30808 AN: 41502

American (AMR) AF: 0.481 AC: 7346 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1150 AN: 3470

East Asian (EAS) AF: 0.584 AC: 2999 AN: 5138

South Asian (SAS) AF: 0.353 AC: 1703 AN: 4818

European-Finnish (FIN) AF: 0.365 AC: 3853 AN: 10556

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.298 AC: 20272 AN: 67954

Other (OTH) AF: 0.442 AC: 930 AN: 2106

Alfa AF: 0.393 Hom.: 1786

Bravo AF: 0.483

Asia WGS AF: 0.501 AC: 1738 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.13
DANN	Benign	0.64
PhyloP100		-2.6
PromoterAI		-0.0042	Neutral

Splicing

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

Other links and lift over

dbSNP: rs1211497; hg19: chr14-103388780;