rs4959677

Positions:

• chr6-2500586-G-C
• chr6-2500586-G-T

Variant summary

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

The ENST00000659523.1(GMDS-DT):​n.621+19417G>C 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 0.424 in 152,104 control chromosomes in the GnomAD database, including 14,584 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 0.42 (14584 hom., cov: 32)
• Consequence: GMDS-DT ENST00000659523.1 intron, non_coding_transcript
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.237

Genes affected

GMDS-DT (HGNC:48993): (GMDS divergent transcript)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.71).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GMDS-DT	ENST00000659523.1	n.621+19417G>C		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.424 AC: 64430 AN: 151986 Hom.: 14585 Cov.: 32

Gnomad AFR AF: 0.275

Gnomad AMI AF: 0.574

Gnomad AMR AF: 0.509

Gnomad ASJ AF: 0.538

Gnomad EAS AF: 0.216

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.488

Gnomad MID AF: 0.487

Gnomad NFE AF: 0.490

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.424 AC: 64455 AN: 152104 Hom.: 14584 Cov.: 32 AF XY: 0.426 AC XY: 31647 AN XY: 74352

Gnomad4 AFR AF: 0.275

Gnomad4 AMR AF: 0.509

Gnomad4 ASJ AF: 0.538

Gnomad4 EAS AF: 0.216

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.488

Gnomad4 NFE AF: 0.490

Gnomad4 OTH AF: 0.456

Alfa AF: 0.432 Hom.: 1790

Bravo AF: 0.420

Asia WGS AF: 0.345 AC: 1203 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	13
DANN	Benign	0.55

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs4959677; hg19: chr6-2500820;