rs4388209

chr5-126422681-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000648070.1(ENSG00000250602):n.896-29051A>G variant causes a intron, non coding transcript 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: ENST00000648070.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.06

Genes affected

(HGNC:):

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

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	UniProt
GRAMD2B	NM_001146319.3	c.129-42745T>C		intron_variant
GRAMD2B	XM_005272057.5	c.126-42745T>C		intron_variant
GRAMD2B	XM_005272058.5	c.126-42745T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000648070.1	n.896-29051A>G		intron_variant, non_coding_transcript_variant
GRAMD2B	ENST00000506445.5	c.126-42745T>C		intron_variant		5
GRAMD2B	ENST00000513040.5	c.129-42745T>C		intron_variant		2

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

Gnomad4 AFR AF: 0.766

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.621

Gnomad4 EAS AF: 0.523

Gnomad4 SAS AF: 0.577

Gnomad4 FIN AF: 0.741

Gnomad4 NFE AF: 0.716

Gnomad4 OTH AF: 0.698

Alfa AF: 0.711 Hom.: 36954

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

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;