14-102929087-G-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.552

Publications

4 publications found

Variant links:

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

AMN links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
AMN	NM_030943.4 link	c.514-34G>C	intron_variant	Intron 5 of 11	ENST00000299155.10	NP_112205.2	Q9BXJ7-1
AMN	NM_001425246.1 link	c.352-34G>C	intron_variant	Intron 5 of 11		NP_001412175.1
AMN	XM_011537203.4 link	c.352-34G>C	intron_variant	Intron 5 of 11		XP_011535505.1	B3KP64

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AMN	ENST00000299155.10 link	c.514-34G>C		intron_variant	Intron 5 of 11	1	NM_030943.4	ENSP00000299155.6		Q9BXJ7-1

Frequencies

GnomAD3 genomes

AF:

0.00437

AC:

665

AN:

152184

Hom.:

Cov.:

show subpopulations

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

show subpopulations

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.:

Cov.:

AF XY:

0.000788

AC XY:

567

AN XY:

719354

show subpopulations

African (AFR)

AF:

0.0163

AC:

544

AN:

33450

American (AMR)

AF:

0.00208

AC:

AN:

44682

Ashkenazi Jewish (ASJ)

AF:

0.000498

AC:

AN:

26094

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86188

European-Finnish (FIN)

AF:

0.000106

AC:

AN:

37612

Middle Eastern (MID)

AF:

0.00191

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.000402

AC:

447

AN:

1111578

Other (OTH)

AF:

0.00178

AC:

107

AN:

60196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

154

232

309

386

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

136

170

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00437

AC:

666

AN:

152302

Hom.:

Cov.:

AF XY:

0.00415

AC XY:

309

AN XY:

74470

show subpopulations

African (AFR)

AF:

0.0140

AC:

582

AN:

41568

American (AMR)

AF:

0.00307

AC:

AN:

15306

Ashkenazi Jewish (ASJ)

AF:

0.000288

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5164

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.0000942

AC:

AN:

10620

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000368

AC:

AN:

68018

Other (OTH)

AF:

0.00425

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

105

140

175

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000297

Hom.:

Bravo

AF:

0.00525

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Imerslund-Grasbeck syndrome type 2

Benign:1

Oct 20, 2023

ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Imerslund-Grasbeck syndrome

Benign:1

Jan 06, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.82

CADD

Benign

2.3

(source)

DANN

Benign

0.58

PhyloP100

-0.55

PromoterAI

0.010

Neutral

(source)

Mutation Taster

=52/34

polymorphism

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over