dbSNP rs532856454: GRAMD1B:p.Ala451Val (chr11-123606637-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_001387025.1(GRAMD1B):c.1352C>T(p.Ala451Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000109 in 1,612,074 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00016 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00010 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.94

Publications

0 publications found

Variant links:

Genes affected

GRAMD1B (HGNC:29214): (GRAM domain containing 1B) Predicted to enable cholesterol binding activity; cholesterol transfer activity; and phospholipid binding activity. Predicted to be involved in cellular response to cholesterol and cholesterol homeostasis. Located in endoplasmic reticulum membrane; endoplasmic reticulum-plasma membrane contact site; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD1B links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.017593384).

BP6

Variant 11-123606637-C-T is Benign according to our data. Variant chr11-123606637-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3282576.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001387025.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRAMD1B	NM_001387025.1	MANE Select	c.1352C>T	p.Ala451Val	missense	Exon 11 of 20	NP_001373954.1	A0A1B0GUD6
GRAMD1B	NM_001387024.1		c.1352C>T	p.Ala451Val	missense	Exon 11 of 20	NP_001373953.1
GRAMD1B	NM_001387026.1		c.1349C>T	p.Ala450Val	missense	Exon 11 of 20	NP_001373955.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.1352C>T	p.Ala451Val	missense	Exon 11 of 20	ENSP00000490062.1	A0A1B0GUD6
GRAMD1B	ENST00000529750.5	TSL:1	c.923C>T	p.Ala308Val	missense	Exon 10 of 20	ENSP00000436500.1	Q3KR37-1
GRAMD1B	ENST00000534764.1	TSL:1	c.911C>T	p.Ala304Val	missense	Exon 10 of 12	ENSP00000434214.1	E9PRD6

Frequencies

GnomAD3 genomes

AF:

0.000158

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000448

AC:

AN:

245784

AF XY:

0.0000375

show subpopulations

Gnomad AFR exome

AF:

0.000331

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000269

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000104

AC:

152

AN:

1459800

Hom.:

Cov.:

AF XY:

0.0000909

AC XY:

AN XY:

725898

show subpopulations

African (AFR)

AF:

0.000359

AC:

AN:

33448

American (AMR)

AF:

0.0000225

AC:

AN:

44516

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26082

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39654

South Asian (SAS)

AF:

0.000105

AC:

AN:

85546

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5718

European-Non Finnish (NFE)

AF:

0.000113

AC:

126

AN:

1111242

Other (OTH)

AF:

0.0000332

AC:

AN:

60312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.455

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

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

GnomAD4 genome

AF:

0.000158

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.000148

AC XY:

AN XY:

74460

show subpopulations

African (AFR)

AF:

0.000481

AC:

AN:

41550

American (AMR)

AF:

0.00

AC:

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5180

South Asian (SAS)

AF:

0.000207

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10600

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

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:

0.0000897

Hom.:

Bravo

AF:

0.000117

ExAC

AF:

0.0000662

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.059

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.61

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0098

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.55

FATHMM_MKL

Benign

0.29

LIST_S2

Benign

0.80

M_CAP

Benign

0.013

MetaRNN

Benign

0.018

MetaSVM

Benign

-1.0

PhyloP100

1.9

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.17

REVEL

Benign

0.035

Sift

Benign

0.56

Sift4G

Benign

0.66

Polyphen

0.0010

Vest4

0.073

MVP

0.043

MPC

0.36

ClinPred

0.033

GERP RS

1.6

Varity_R

0.022

gMVP

0.27

Mutation Taster

=97/3

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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