Genetic Variant GRAMD1B:p.Asp415Glu (chr11-123605400-T-A) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001387025.1(GRAMD1B):c.1245T>A(p.Asp415Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00073 in 1,613,430 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0039 ( 6 hom., cov: 32)

Exomes 𝑓: 0.00040 ( 4 hom. )

Consequence

GRAMD1B
NM_001387025.1 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.414

Publications

2 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0047641993).

BP6

Variant 11-123605400-T-A is Benign according to our data. Variant chr11-123605400-T-A is described in ClinVar as Benign. ClinVar VariationId is 791359.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

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.1245T>A	p.Asp415Glu	missense	Exon 10 of 20	NP_001373954.1	A0A1B0GUD6
GRAMD1B	NM_001387024.1		c.1245T>A	p.Asp415Glu	missense	Exon 10 of 20	NP_001373953.1
GRAMD1B	NM_001387026.1		c.1242T>A	p.Asp414Glu	missense	Exon 10 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.1245T>A	p.Asp415Glu	missense	Exon 10 of 20	ENSP00000490062.1	A0A1B0GUD6
GRAMD1B	ENST00000529750.5	TSL:1	c.816T>A	p.Asp272Glu	missense	Exon 9 of 20	ENSP00000436500.1	Q3KR37-1
GRAMD1B	ENST00000534764.1	TSL:1	c.804T>A	p.Asp268Glu	missense	Exon 9 of 12	ENSP00000434214.1	E9PRD6

Frequencies

GnomAD3 genomes

AF:

0.00391

AC:

594

AN:

152080

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0129

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00287

GnomAD2 exomes

AF:

0.00101

AC:

252

AN:

248898

AF XY:

0.000770

show subpopulations

Gnomad AFR exome

AF:

0.0131

Gnomad AMR exome

AF:

0.00105

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000620

Gnomad OTH exome

AF:

0.000996

GnomAD4 exome

AF:

0.000396

AC:

578

AN:

1461232

Hom.:

Cov.:

AF XY:

0.000377

AC XY:

274

AN XY:

726892

show subpopulations

African (AFR)

AF:

0.0130

AC:

435

AN:

33454

American (AMR)

AF:

0.00125

AC:

AN:

44702

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26118

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.00

AC:

AN:

86202

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53400

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5762

European-Non Finnish (NFE)

AF:

0.0000189

AC:

AN:

1111538

Other (OTH)

AF:

0.000994

AC:

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.490

Heterozygous variant carriers

111

139

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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:

0.00394

AC:

599

AN:

152198

Hom.:

Cov.:

AF XY:

0.00391

AC XY:

291

AN XY:

74422

show subpopulations

African (AFR)

AF:

0.0130

AC:

538

AN:

41526

American (AMR)

AF:

0.00327

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4812

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

67994

Other (OTH)

AF:

0.00284

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

108

135

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:

0.000535

Hom.:

Bravo

AF:

0.00456

ESP6500AA

AF:

0.0127

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00116

AC:

141

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000238

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.66

BayesDel_noAF

Benign

-0.71

CADD

Benign

2.3

(source)

DANN

Benign

0.49

DEOGEN2

Benign

0.0028

Eigen

Benign

-0.92

Eigen_PC

Benign

-0.72

FATHMM_MKL

Benign

0.38

LIST_S2

Uncertain

0.88

MetaRNN

Benign

0.0048

MetaSVM

Benign

-1.0

PhyloP100

-0.41

PrimateAI

Uncertain

0.54

PROVEAN

Benign

1.1

REVEL

Benign

0.21

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.056

MutPred

0.12

Gain of methylation at K277 (P = 0.1556)

MVP

0.043

MPC

0.34

ClinPred

0.0056

GERP RS

2.7

Varity_R

0.041

gMVP

0.14

Mutation Taster

=100/0

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