chr5-126422681-T-C

Variant names:

• chr5-126422681-T-C
• rs4388209
• NM_001146319.3:c.129-42745T>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.759 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GRAMD2B	NM_001146319.3	c.129-42745T>C		intron_variant	Intron 1 of 13		NP_001139791.1
GRAMD2B	XM_011543593.3	c.129-42745T>C		intron_variant	Intron 1 of 13		XP_011541895.1
GRAMD2B	XM_005272057.5	c.126-42745T>C		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.129-42745T>C		intron_variant	Intron 1 of 13	2		ENSP00000426120.1
GRAMD2B	ENST00000506445.5	c.126-42745T>C		intron_variant	Intron 1 of 8	5		ENSP00000424985.1
ENSG00000250602	ENST00000648070.1	n.896-29051A>G		intron_variant	Intron 2 of 3

Frequencies

GnomAD3 genomes AF: 0.720 AC: 109414 AN: 151946 Hom.: 39847 Cov.: 32

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.: 32 AF XY: 0.718 AC XY: 53374 AN XY: 74332

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.25
DANN	Benign	0.43
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4388209; hg19: chr5-125758373;