Genetic Variant GRAMD2B:c.129-42745T>C (chr5-126422681-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001146319.3(GRAMD2B):c.129-42745T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.72 in 152,064 control chromosomes in the GnomAD database, including 39,902 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.72 ( 39902 hom., cov: 32)

Consequence

GRAMD2B
NM_001146319.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.06

Publications

2 publications found

Variant links:

Genes affected

GRAMD2B (HGNC:24911): (GRAM domain containing 2B) Enables identical protein binding activity. Located in cytoplasmic microtubule. [provided by Alliance of Genome Resources, Apr 2022]

GRAMD2B links:

ENSG00000250602 (HGNC:41069):

ENSG00000250602 links:

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new If you want to explore the variant's impact on the transcript NM_001146319.3, 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 -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001146319.3. 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
	GRAMD2B	NM_001146319.3		c.129-42745T>C		intron	N/A	NP_001139791.1	Q96HH9-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GRAMD2B	ENST00000513040.5	TSL:2	c.129-42745T>C	intron	N/A	ENSP00000426120.1	Q96HH9-3
GRAMD2B	ENST00000506445.5	TSL:5	c.126-42745T>C	intron	N/A	ENSP00000424985.1	D6REP5
ENSG00000250602	ENST00000648070.1		n.896-29051A>G	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.720

AC:

109414

AN:

151946

Hom.:

39847

Cov.:

show subpopulations

Gnomad AFR

AF:

0.766

Gnomad AMI

AF:

0.768

Gnomad AMR

AF:

0.737

Gnomad ASJ

AF:

0.621

Gnomad EAS

AF:

0.522

Gnomad SAS

AF:

0.577

Gnomad FIN

AF:

0.741

Gnomad MID

AF:

0.554

Gnomad NFE

AF:

0.716

Gnomad OTH

AF:

0.702

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.720

AC:

109529

AN:

152064

Hom.:

39902

Cov.:

AF XY:

0.718

AC XY:

53374

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.766

AC:

31771

AN:

41476

American (AMR)

AF:

0.737

AC:

11256

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.621

AC:

2150

AN:

3464

East Asian (EAS)

AF:

0.523

AC:

2701

AN:

5168

South Asian (SAS)

AF:

0.577

AC:

2780

AN:

4814

European-Finnish (FIN)

AF:

0.741

AC:

7829

AN:

10572

Middle Eastern (MID)

AF:

0.565

AC:

165

AN:

292

European-Non Finnish (NFE)

AF:

0.716

AC:

48703

AN:

67974

Other (OTH)

AF:

0.698

AC:

1475

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

1523

3046

4570

6093

7616

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

834

1668

2502

3336

4170

<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:

0.712

Hom.:

54963

Bravo

AF:

0.724

Asia WGS

AF:

0.561

AC:

1952

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.25

(source)

DANN

Benign

0.43

PhyloP100

-1.1

PromoterAI

0.012

Neutral

(source)

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over