14-102922666-G-C

Variant names:

• chr14-102922666-G-C
• rs2295829
• NM_030943.4:c.-23G>C

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.-23G>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 1,592,304 control chromosomes in the GnomAD database, including 123,872 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (14519 hom., cov: 32)
  • Exomes 𝑓: 0.38 (109353 hom.)
• Consequence: AMN NM_030943.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.64
• Publications: 11 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=-0.84).
• BP6: Variant 14-102922666-G-C is Benign according to our data. Variant chr14-102922666-G-C is described in ClinVar as Benign. ClinVar VariationId is 1262486.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.558 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.-23G>C		5_prime_UTR	Exon 1 of 12	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-204G>C		5_prime_UTR	Exon 1 of 12	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.-23G>C		5_prime_UTR	Exon 1 of 12	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.-23G>C		upstream_gene	N/A	ENSP00000543058.1

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64384 AN: 151722 Hom.: 14493 Cov.: 32

Gnomad AFR AF: 0.564

Gnomad AMI AF: 0.440

Gnomad AMR AF: 0.382

Gnomad ASJ AF: 0.369

Gnomad EAS AF: 0.107

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.349

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.399

Gnomad OTH AF: 0.400

GnomAD2 exomes AF: 0.343 AC: 74710 AN: 217602 AF XY: 0.342

Gnomad AFR exome AF: 0.555

Gnomad AMR exome AF: 0.308

Gnomad ASJ exome AF: 0.375

Gnomad EAS exome AF: 0.0940

Gnomad FIN exome AF: 0.333

Gnomad NFE exome AF: 0.383

Gnomad OTH exome AF: 0.370

GnomAD4 exome AF: 0.384 AC: 553364 AN: 1440464 Hom.: 109353 Cov.: 37 AF XY: 0.381 AC XY: 272199 AN XY: 714976

African (AFR) AF: 0.569 AC: 18942 AN: 33306

American (AMR) AF: 0.320 AC: 13419 AN: 41998

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 9634 AN: 25682

East Asian (EAS) AF: 0.111 AC: 4355 AN: 39224

South Asian (SAS) AF: 0.296 AC: 24628 AN: 83304

European-Finnish (FIN) AF: 0.356 AC: 16891 AN: 47426

Middle Eastern (MID) AF: 0.388 AC: 2112 AN: 5448

European-Non Finnish (NFE) AF: 0.399 AC: 440476 AN: 1104402

Other (OTH) AF: 0.384 AC: 22907 AN: 59674

GnomAD4 genome AF: 0.425 AC: 64469 AN: 151840 Hom.: 14519 Cov.: 32 AF XY: 0.419 AC XY: 31068 AN XY: 74216

African (AFR) AF: 0.564 AC: 23362 AN: 41392

American (AMR) AF: 0.382 AC: 5834 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.369 AC: 1279 AN: 3466

East Asian (EAS) AF: 0.107 AC: 552 AN: 5162

South Asian (SAS) AF: 0.280 AC: 1346 AN: 4814

European-Finnish (FIN) AF: 0.349 AC: 3684 AN: 10558

Middle Eastern (MID) AF: 0.373 AC: 109 AN: 292

European-Non Finnish (NFE) AF: 0.399 AC: 27064 AN: 67868

Other (OTH) AF: 0.397 AC: 838 AN: 2110

Alfa AF: 0.296 Hom.: 993

Bravo AF: 0.434

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	-0.84
CADD	Benign	1.4
DANN	Benign	0.55
PhyloP100		-1.6
PromoterAI		0.34	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=300/0	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: rs2295829; hg19: chr14-103389003; COSMIC: COSV54486859; COSMIC: COSV54486859;