chr5-126402275-A-G

Variant names:

• chr5-126402275-A-G
• rs4836255
• NM_001146319.3:c.128+41816A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001146319.3(GRAMD2B):​c.128+41816A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.958 in 152,188 control chromosomes in the GnomAD database, including 69,843 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 0.96 (69843 hom., cov: 32)
• Consequence: GRAMD2B NM_001146319.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.503
• Publications: 3 publications found

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]

ENSG00000250602 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD2B	NM_001146319.3	c.128+41816A>G		intron_variant	Intron 1 of 13		NP_001139791.1
GRAMD2B	XM_011543593.3	c.128+41816A>G		intron_variant	Intron 1 of 13		XP_011541895.1
GRAMD2B	XM_005272057.5	c.125+30708A>G		intron_variant	Intron 1 of 13		XP_005272114.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GRAMD2B	ENST00000513040.5	c.128+41816A>G		intron_variant	Intron 1 of 13	2		ENSP00000426120.1
GRAMD2B	ENST00000506445.5	c.125+30708A>G		intron_variant	Intron 1 of 8	5		ENSP00000424985.1
ENSG00000250602	ENST00000648070.1	n.896-8645T>C		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.958 AC: 145682 AN: 152070 Hom.: 69791 Cov.: 32

Gnomad AFR AF: 0.937

Gnomad AMI AF: 0.974

Gnomad AMR AF: 0.958

Gnomad ASJ AF: 0.968

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.986

Gnomad FIN AF: 0.983

Gnomad MID AF: 0.937

Gnomad NFE AF: 0.961

Gnomad OTH AF: 0.958

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

GnomAD4 genome AF: 0.958 AC: 145793 AN: 152188 Hom.: 69843 Cov.: 32 AF XY: 0.959 AC XY: 71388 AN XY: 74424

African (AFR) AF: 0.937 AC: 38914 AN: 41526

American (AMR) AF: 0.958 AC: 14629 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.968 AC: 3355 AN: 3466

East Asian (EAS) AF: 1.00 AC: 5165 AN: 5166

South Asian (SAS) AF: 0.985 AC: 4757 AN: 4828

European-Finnish (FIN) AF: 0.983 AC: 10444 AN: 10628

Middle Eastern (MID) AF: 0.935 AC: 275 AN: 294

European-Non Finnish (NFE) AF: 0.961 AC: 65341 AN: 67988

Other (OTH) AF: 0.959 AC: 2025 AN: 2112

Alfa AF: 0.958 Hom.: 14872

Bravo AF: 0.955

Asia WGS AF: 0.991 AC: 3446 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	2.6
DANN	Benign	0.86
PhyloP100		-0.50
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs4836255; hg19: chr5-125737967;