rs1190228

Variant names:

• chr14-102925406-A-G
• rs1190228
• NM_030943.4:c.207+1427A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-102925406-A-G
• chr14-102925406-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_030943.4(AMN):​c.207+1427A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.673 in 152,144 control chromosomes in the GnomAD database, including 35,691 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 0.67 (35691 hom., cov: 33)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 1 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.95).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4	c.207+1427A>G		intron_variant	Intron 3 of 11	ENST00000299155.10	NP_112205.2
AMN	NM_001425246.1	c.45+1427A>G		intron_variant	Intron 3 of 11		NP_001412175.1
AMN	XM_011537203.4	c.45+1427A>G		intron_variant	Intron 3 of 11		XP_011535505.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10	c.207+1427A>G		intron_variant	Intron 3 of 11	1	NM_030943.4	ENSP00000299155.6
AMN	ENST00000541086.5	n.953+1427A>G		intron_variant	Intron 2 of 10	2

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102269 AN: 152028 Hom.: 35628 Cov.: 33

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.740

Gnomad AMR AF: 0.657

Gnomad ASJ AF: 0.667

Gnomad EAS AF: 0.480

Gnomad SAS AF: 0.538

Gnomad FIN AF: 0.624

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.591

Gnomad OTH AF: 0.659

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

GnomAD4 genome AF: 0.673 AC: 102387 AN: 152144 Hom.: 35691 Cov.: 33 AF XY: 0.672 AC XY: 49963 AN XY: 74384

African (AFR) AF: 0.865 AC: 35907 AN: 41518

American (AMR) AF: 0.658 AC: 10061 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.667 AC: 2313 AN: 3470

East Asian (EAS) AF: 0.480 AC: 2476 AN: 5162

South Asian (SAS) AF: 0.538 AC: 2595 AN: 4824

European-Finnish (FIN) AF: 0.624 AC: 6606 AN: 10582

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.591 AC: 40194 AN: 67976

Other (OTH) AF: 0.656 AC: 1385 AN: 2112

Alfa AF: 0.644 Hom.: 3997

Bravo AF: 0.688

Asia WGS AF: 0.570 AC: 1984 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	3.0
DANN	Benign	0.36
PhyloP100		-0.38
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: rs1190228; hg19: chr14-103391743;