14-102922602-C-G

Variant names:

• chr14-102922602-C-G
• rs59793431
• NM_030943.4:c.-87C>G

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.-87C>G variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.115 in 1,493,412 control chromosomes in the GnomAD database, including 15,688 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (5467 hom., cov: 32)
  • Exomes 𝑓: 0.11 (10221 hom.)
• Consequence: AMN NM_030943.4 upstream_gene
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.04
• Publications: 3 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=-0.82).
• BP6: Variant 14-102922602-C-G is Benign according to our data. Variant chr14-102922602-C-G is described in ClinVar as Benign. ClinVar VariationId is 1286303.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.47 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	NM_030943.4	MANE Select	c.-87C>G		upstream_gene	N/A	NP_112205.2
	AMN	NM_001425246.1		c.-268C>G		upstream_gene	N/A	NP_001412175.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AMN	ENST00000299155.10	TSL:1 MANE Select	c.-87C>G		upstream_gene	N/A	ENSP00000299155.6
	AMN	ENST00000872999.1		c.-87C>G		upstream_gene	N/A	ENSP00000543058.1

Frequencies

GnomAD3 genomes AF: 0.203 AC: 30883 AN: 151948 Hom.: 5442 Cov.: 32

Gnomad AFR AF: 0.475

Gnomad AMI AF: 0.185

Gnomad AMR AF: 0.137

Gnomad ASJ AF: 0.0936

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0736

Gnomad FIN AF: 0.0945

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.170

GnomAD4 exome AF: 0.105 AC: 141322 AN: 1341346 Hom.: 10221 AF XY: 0.103 AC XY: 68396 AN XY: 661784

African (AFR) AF: 0.490 AC: 15074 AN: 30736

American (AMR) AF: 0.115 AC: 4076 AN: 35334

Ashkenazi Jewish (ASJ) AF: 0.0967 AC: 2350 AN: 24294

East Asian (EAS) AF: 0.000901 AC: 33 AN: 36620

South Asian (SAS) AF: 0.0798 AC: 6190 AN: 77582

European-Finnish (FIN) AF: 0.0940 AC: 3437 AN: 36558

Middle Eastern (MID) AF: 0.121 AC: 628 AN: 5206

European-Non Finnish (NFE) AF: 0.0991 AC: 102991 AN: 1038846

Other (OTH) AF: 0.116 AC: 6543 AN: 56170

GnomAD4 genome AF: 0.204 AC: 30962 AN: 152066 Hom.: 5467 Cov.: 32 AF XY: 0.199 AC XY: 14776 AN XY: 74362

African (AFR) AF: 0.475 AC: 19690 AN: 41430

American (AMR) AF: 0.138 AC: 2105 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.0936 AC: 325 AN: 3472

East Asian (EAS) AF: 0.00193 AC: 10 AN: 5184

South Asian (SAS) AF: 0.0729 AC: 351 AN: 4818

European-Finnish (FIN) AF: 0.0945 AC: 1001 AN: 10594

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.102 AC: 6918 AN: 67958

Other (OTH) AF: 0.169 AC: 356 AN: 2110

Alfa AF: 0.0527 Hom.: 64

Bravo AF: 0.221

Asia WGS AF: 0.0700 AC: 245 AN: 3478

ClinVar

ClinVar submissions as Germline

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	-0.82
CADD	Benign	3.7
DANN	Benign	0.75
PhyloP100		-1.0
PromoterAI		-0.22	Neutral

Splicing

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

Other links and lift over

dbSNP: rs59793431; hg19: chr14-103388939; COSMIC: COSV54486850;