rs2295828

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_030943.4(AMN):c.-27T>C variant causes a upstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.473 in 1,590,276 control chromosomes in the GnomAD database, including 180,463 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.47 ( 17105 hom., cov: 31)

Exomes 𝑓: 0.47 ( 163358 hom. )

Consequence

AMN
NM_030943.4 upstream_gene

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.15

Publications

13 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

new If you want to explore the variant's impact on the transcript NM_030943.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.84).

BP6

Variant 14-102922662-T-C is Benign according to our data. Variant chr14-102922662-T-C is described in ClinVar as Benign. ClinVar VariationId is 1243841.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.501 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.-27T>C		upstream_gene	N/A	NP_112205.2	Q9BXJ7-1
	AMN	NM_001425246.1		c.-208T>C		upstream_gene	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.-27T>C		upstream_gene	N/A	ENSP00000299155.6	Q9BXJ7-1
	AMN	ENST00000872999.1		c.-27T>C		upstream_gene	N/A	ENSP00000543058.1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71397

AN:

151614

Hom.:

17085

Cov.:

show subpopulations

Gnomad AFR

AF:

0.470

Gnomad AMI

AF:

0.615

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.495

Gnomad EAS

AF:

0.212

Gnomad SAS

AF:

0.369

Gnomad FIN

AF:

0.458

Gnomad MID

AF:

0.472

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.475

GnomAD2 exomes

AF:

0.440

AC:

94665

AN:

215196

AF XY:

0.436

show subpopulations

Gnomad AFR exome

AF:

0.453

Gnomad AMR exome

AF:

0.503

Gnomad ASJ exome

AF:

0.501

Gnomad EAS exome

AF:

0.192

Gnomad FIN exome

AF:

0.427

Gnomad NFE exome

AF:

0.476

Gnomad OTH exome

AF:

0.461

GnomAD4 exome

AF:

0.473

AC:

680874

AN:

1438544

Hom.:

163358

Cov.:

AF XY:

0.470

AC XY:

335748

AN XY:

713938

show subpopulations

African (AFR)

AF:

0.459

AC:

15277

AN:

33272

American (AMR)

AF:

0.507

AC:

21135

AN:

41658

Ashkenazi Jewish (ASJ)

AF:

0.505

AC:

12956

AN:

25636

East Asian (EAS)

AF:

0.237

AC:

9270

AN:

39194

South Asian (SAS)

AF:

0.380

AC:

31626

AN:

83160

European-Finnish (FIN)

AF:

0.450

AC:

21154

AN:

47014

Middle Eastern (MID)

AF:

0.478

AC:

2601

AN:

5446

European-Non Finnish (NFE)

AF:

0.488

AC:

539074

AN:

1103546

Other (OTH)

AF:

0.466

AC:

27781

AN:

59618

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

18240

36480

54720

72960

91200

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15740

31480

47220

62960

78700

<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:

0.471

AC:

71462

AN:

151732

Hom.:

17105

Cov.:

AF XY:

0.469

AC XY:

34772

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.470

AC:

19459

AN:

41386

American (AMR)

AF:

0.510

AC:

7786

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.495

AC:

1714

AN:

3464

East Asian (EAS)

AF:

0.213

AC:

1091

AN:

5132

South Asian (SAS)

AF:

0.369

AC:

1774

AN:

4810

European-Finnish (FIN)

AF:

0.458

AC:

4823

AN:

10526

Middle Eastern (MID)

AF:

0.480

AC:

141

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33119

AN:

67834

Other (OTH)

AF:

0.471

AC:

994

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1921

3842

5763

7684

9605

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

634

1268

1902

2536

3170

<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:

0.427

Hom.:

2941

Bravo

AF:

0.478

Asia WGS

AF:

0.346

AC:

1203

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.086

(source)

DANN

Benign

0.48

PhyloP100

-3.1

PromoterAI

0.064

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=300/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over