rs6721434

Positions:

• chr2-25446648-G-A

Variant summary

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

The NM_021907.5(DTNB):​c.1257+4900C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.847 in 152,098 control chromosomes in the GnomAD database, including 54,810 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 0.85 (54810 hom., cov: 30)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.66

Genes affected

DTNB (HGNC:3058): (dystrobrevin beta) This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin. [provided by RefSeq, Mar 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.867 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNB	NM_021907.5	c.1257+4900C>T		intron_variant		ENST00000406818.8	NP_068707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8	c.1257+4900C>T		intron_variant		1	NM_021907.5	ENSP00000384084	P4

Frequencies

GnomAD3 genomes AF: 0.847 AC: 128692 AN: 151980 Hom.: 54764 Cov.: 30

Gnomad AFR AF: 0.854

Gnomad AMI AF: 0.876

Gnomad AMR AF: 0.712

Gnomad ASJ AF: 0.882

Gnomad EAS AF: 0.742

Gnomad SAS AF: 0.818

Gnomad FIN AF: 0.899

Gnomad MID AF: 0.842

Gnomad NFE AF: 0.873

Gnomad OTH AF: 0.829

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

GnomAD4 genome AF: 0.847 AC: 128791 AN: 152098 Hom.: 54810 Cov.: 30 AF XY: 0.844 AC XY: 62743 AN XY: 74352

Gnomad4 AFR AF: 0.854

Gnomad4 AMR AF: 0.712

Gnomad4 ASJ AF: 0.882

Gnomad4 EAS AF: 0.742

Gnomad4 SAS AF: 0.818

Gnomad4 FIN AF: 0.899

Gnomad4 NFE AF: 0.873

Gnomad4 OTH AF: 0.829

Alfa AF: 0.866 Hom.: 24884

Bravo AF: 0.835

Asia WGS AF: 0.795 AC: 2766 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.22
DANN	Benign	0.31

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6721434; hg19: chr2-25669517;