rs1190225

Variant names:

• chr14-102922877-C-T
• rs1190225
• NM_030943.4:c.43+146C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-102922877-C-T
• chr14-102922877-C-A

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.43+146C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0705 in 1,149,760 control chromosomes in the GnomAD database, including 3,266 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.058 (314 hom., cov: 33)
  • Exomes 𝑓: 0.072 (2952 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.39
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 14-102922877-C-T is Benign according to our data. Variant chr14-102922877-C-T is described in ClinVar as Benign. ClinVar VariationId is 1268789.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.117 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.43+146C>T		intron	N/A	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-120+127C>T		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.43+146C>T		intron	N/A	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.43+146C>T		intron	N/A	ENSP00000543058.1
	AMN	ENST00000541086.5	TSL:2	n.-45C>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.0578 AC: 8795 AN: 152170 Hom.: 314 Cov.: 33

Gnomad AFR AF: 0.0304

Gnomad AMI AF: 0.0757

Gnomad AMR AF: 0.0434

Gnomad ASJ AF: 0.0599

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.0429

Gnomad FIN AF: 0.0617

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0731

Gnomad OTH AF: 0.0516

GnomAD4 exome AF: 0.0724 AC: 72221 AN: 997472 Hom.: 2952 Cov.: 13 AF XY: 0.0710 AC XY: 35104 AN XY: 494376

African (AFR) AF: 0.0257 AC: 595 AN: 23112

American (AMR) AF: 0.0309 AC: 873 AN: 28208

Ashkenazi Jewish (ASJ) AF: 0.0660 AC: 1237 AN: 18736

East Asian (EAS) AF: 0.159 AC: 5054 AN: 31872

South Asian (SAS) AF: 0.0440 AC: 2685 AN: 61046

European-Finnish (FIN) AF: 0.0702 AC: 2162 AN: 30788

Middle Eastern (MID) AF: 0.0331 AC: 102 AN: 3080

European-Non Finnish (NFE) AF: 0.0748 AC: 56617 AN: 756512

Other (OTH) AF: 0.0656 AC: 2896 AN: 44118

GnomAD4 genome AF: 0.0578 AC: 8798 AN: 152288 Hom.: 314 Cov.: 33 AF XY: 0.0590 AC XY: 4397 AN XY: 74472

African (AFR) AF: 0.0304 AC: 1263 AN: 41570

American (AMR) AF: 0.0434 AC: 663 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0599 AC: 208 AN: 3472

East Asian (EAS) AF: 0.125 AC: 648 AN: 5170

South Asian (SAS) AF: 0.0431 AC: 208 AN: 4826

European-Finnish (FIN) AF: 0.0617 AC: 656 AN: 10626

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0731 AC: 4971 AN: 68010

Other (OTH) AF: 0.0516 AC: 109 AN: 2114

Alfa AF: 0.0660 Hom.: 126

Bravo AF: 0.0565

Asia WGS AF: 0.0730 AC: 254 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.80
DANN	Benign	0.43
PhyloP100		-1.4
PromoterAI		-0.19	Neutral
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: rs1190225; hg19: chr14-103389214; COSMIC: COSV54488105; COSMIC: COSV54488105;