dbSNP rs373483380: GRAMD1B:c.664-8C>T (chr11-123584304-C-T) – ACMG Classification: Likely_benign (-5 pts)

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4_StrongBP6

The NM_001387025.1(GRAMD1B):c.664-8C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (no stars).

Frequency

Genomes: 𝑓 0.00018 ( 0 hom., cov: 0)

Exomes 𝑓: 0.000012 ( 0 hom. )

Consequence

GRAMD1B
NM_001387025.1 splice_region, intron

Scores

Splicing: ADA: 0.00002781

Clinical Significance

Likely benign no assertion criteria provided B:1

Conservation

PhyloP100: 0.296

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 -5 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.54).

BP6

Variant 11-123584304-C-T is Benign according to our data. Variant chr11-123584304-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3056394.Status of the report is no_assertion_criteria_provided, 0 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	Effect	Exon Rank	Protein	UniProt
GRAMD1B	NM_001387025.1	MANE Select	c.664-8C>T	splice_region intron	N/A	NP_001373954.1	A0A1B0GUD6
GRAMD1B	NM_001387024.1		c.664-8C>T	splice_region intron	N/A	NP_001373953.1
GRAMD1B	NM_001387026.1		c.661-8C>T	splice_region intron	N/A	NP_001373955.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRAMD1B	ENST00000635736.2	TSL:5 MANE Select	c.664-8C>T	splice_region intron	N/A	ENSP00000490062.1	A0A1B0GUD6
GRAMD1B	ENST00000529750.5	TSL:1	c.235-8C>T	splice_region intron	N/A	ENSP00000436500.1	Q3KR37-1
GRAMD1B	ENST00000534764.1	TSL:1	c.223-8C>T	splice_region intron	N/A	ENSP00000434214.1	E9PRD6

Frequencies

GnomAD3 genomes

AF:

0.000183

AC:

AN:

10910

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00275

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00794

GnomAD2 exomes

AF:

0.0000259

AC:

AN:

154670

AF XY:

0.0000237

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000239

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000296

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000115

AC:

AN:

1042036

Hom.:

Cov.:

AF XY:

0.00000963

AC XY:

AN XY:

518982

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

21732

American (AMR)

AF:

0.00

AC:

AN:

29422

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16036

East Asian (EAS)

AF:

0.000409

AC:

AN:

17122

South Asian (SAS)

AF:

0.0000149

AC:

AN:

67222

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34034

Middle Eastern (MID)

AF:

0.000713

AC:

AN:

4208

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

813444

Other (OTH)

AF:

0.0000258

AC:

AN:

38816

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.442

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:

0.000182

AC:

AN:

10966

Hom.:

Cov.:

AF XY:

0.000357

AC XY:

AN XY:

5608

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

2828

American (AMR)

AF:

0.00

AC:

AN:

766

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

204

East Asian (EAS)

AF:

0.00273

AC:

AN:

366

South Asian (SAS)

AF:

0.00

AC:

AN:

194

European-Finnish (FIN)

AF:

0.00

AC:

AN:

702

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

5640

Other (OTH)

AF:

0.00746

AC:

AN:

134

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

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:

0.00

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

GRAMD1B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.54

CADD

Benign

4.1

(source)

DANN

Benign

0.42

PhyloP100

0.30

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.000028

dbscSNV1_RF

Benign

0.0020

SpliceAI score (max)

0.010

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