14-102925912-A-G

Variant names:

• chr14-102925912-A-G
• rs1190229
• NM_030943.4:c.207+1933A>G

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+1933A>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 152,036 control chromosomes in the GnomAD database, including 35,516 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 (35516 hom., cov: 31)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.25
• 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.841 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.207+1933A>G		intron	N/A	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.45+1933A>G		intron	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.207+1933A>G		intron	N/A	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.150+1933A>G		intron	N/A	ENSP00000543058.1
	AMN	ENST00000541086.5	TSL:2	n.953+1933A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.673 AC: 102247 AN: 151918 Hom.: 35456 Cov.: 31

Gnomad AFR AF: 0.849

Gnomad AMI AF: 0.742

Gnomad AMR AF: 0.660

Gnomad ASJ AF: 0.668

Gnomad EAS AF: 0.478

Gnomad SAS AF: 0.541

Gnomad FIN AF: 0.629

Gnomad MID AF: 0.595

Gnomad NFE AF: 0.600

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.673 AC: 102363 AN: 152036 Hom.: 35516 Cov.: 31 AF XY: 0.672 AC XY: 49961 AN XY: 74318

African (AFR) AF: 0.849 AC: 35199 AN: 41468

American (AMR) AF: 0.661 AC: 10095 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.668 AC: 2318 AN: 3470

East Asian (EAS) AF: 0.478 AC: 2456 AN: 5142

South Asian (SAS) AF: 0.540 AC: 2605 AN: 4820

European-Finnish (FIN) AF: 0.629 AC: 6653 AN: 10578

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

European-Non Finnish (NFE) AF: 0.600 AC: 40796 AN: 67962

Other (OTH) AF: 0.658 AC: 1391 AN: 2114

Alfa AF: 0.626 Hom.: 81513

Bravo AF: 0.688

Asia WGS AF: 0.576 AC: 2003 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.63
DANN	Benign	0.27
PhyloP100		-1.2
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: rs1190229; hg19: chr14-103392249;