14-102929087-G-C

Variant names:

• chr14-102929087-G-C
• rs144077391
• NM_030943.4:c.514-34G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_030943.4(AMN):​c.514-34G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00118 in 1,597,548 control chromosomes in the GnomAD database, including 11 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0044 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00084 (7 hom.)
• Consequence: AMN NM_030943.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.552
• Publications: 4 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 14-102929087-G-C is Benign according to our data. Variant chr14-102929087-G-C is described in ClinVar as Benign. ClinVar VariationId is 1657935.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00437 (666/152302) while in subpopulation AFR AF = 0.014 (582/41568). AF 95% confidence interval is 0.0131. There are 4 homozygotes in GnomAd4. There are 309 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

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.514-34G>C		intron	N/A	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.352-34G>C		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.514-34G>C		intron	N/A	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.457-34G>C		intron	N/A	ENSP00000543058.1
	AMN	ENST00000559789.1	TSL:3	c.124+132G>C		intron	N/A	ENSP00000452831.1	H0YKJ5

Frequencies

GnomAD3 genomes AF: 0.00437 AC: 665 AN: 152184 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0140

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00307

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000368

Gnomad OTH AF: 0.00430

GnomAD2 exomes AF: 0.00150 AC: 333 AN: 222038 AF XY: 0.00116

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.00182

Gnomad ASJ exome AF: 0.000837

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000438

Gnomad OTH exome AF: 0.00212

GnomAD4 exome AF: 0.000845 AC: 1221 AN: 1445246 Hom.: 7 Cov.: 33 AF XY: 0.000788 AC XY: 567 AN XY: 719354

African (AFR) AF: 0.0163 AC: 544 AN: 33450

American (AMR) AF: 0.00208 AC: 93 AN: 44682

Ashkenazi Jewish (ASJ) AF: 0.000498 AC: 13 AN: 26094

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39684

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86188

European-Finnish (FIN) AF: 0.000106 AC: 4 AN: 37612

Middle Eastern (MID) AF: 0.00191 AC: 11 AN: 5762

European-Non Finnish (NFE) AF: 0.000402 AC: 447 AN: 1111578

Other (OTH) AF: 0.00178 AC: 107 AN: 60196

GnomAD4 genome AF: 0.00437 AC: 666 AN: 152302 Hom.: 4 Cov.: 33 AF XY: 0.00415 AC XY: 309 AN XY: 74470

African (AFR) AF: 0.0140 AC: 582 AN: 41568

American (AMR) AF: 0.00307 AC: 47 AN: 15306

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.00 AC: 0 AN: 4834

European-Finnish (FIN) AF: 0.0000942 AC: 1 AN: 10620

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000368 AC: 25 AN: 68018

Other (OTH) AF: 0.00425 AC: 9 AN: 2116

Alfa AF: 0.000297 Hom.: 0

Bravo AF: 0.00525

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Imerslund-Grasbeck syndrome (1)
-	-	1	Imerslund-Grasbeck syndrome type 2 (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.3
DANN	Benign	0.58
PhyloP100		-0.55
PromoterAI		0.010	Neutral
Mutation Taster		=52/34	polymorphism

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: rs144077391; hg19: chr14-103395424;