rs10090787

chr8-120798309-C-T

Variant summary

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

The NM_021021.4(SNTB1):c.571+12964G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,792 control chromosomes in the GnomAD database, including 9,253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

• Frequency: Genomes: 𝑓 0.34 (9253 hom., cov: 32)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: association criteria provided, single submitter O:1
• Conservation: PhyloP100: -1.32

Genes affected

SNTB1 (HGNC:11168): (syntrophin beta 1) Dystrophin is a large, rod-like cytoskeletal protein found at the inner surface of muscle fibers. Dystrophin is missing in Duchenne Muscular Dystrophy patients and is present in reduced amounts in Becker Muscular Dystrophy patients. The protein encoded by this gene is a peripheral membrane protein found associated with dystrophin and dystrophin-related proteins. This gene is a member of the syntrophin gene family, which contains at least two other structurally-related genes. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.437 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNTB1	NM_021021.4	c.571+12964G>A		intron_variant		ENST00000517992.2
SNTB1	XM_011517239.3	c.571+12964G>A		intron_variant
SNTB1	XM_047422126.1	c.-9+4475G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTB1	ENST00000517992.2	c.571+12964G>A		intron_variant		1	NM_021021.4	P1
SNTB1	ENST00000519177.5	n.291+12964G>A		intron_variant, non_coding_transcript_variant		1
SNTB1	ENST00000395601.7	c.571+12964G>A		intron_variant		5		P1
SNTB1	ENST00000648490.1	c.571+12964G>A		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51551 AN: 151674 Hom.: 9228 Cov.: 32

Gnomad AFR AF: 0.442

Gnomad AMI AF: 0.496

Gnomad AMR AF: 0.291

Gnomad ASJ AF: 0.283

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.326

Gnomad FIN AF: 0.362

Gnomad MID AF: 0.411

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.340 AC: 51629 AN: 151792 Hom.: 9253 Cov.: 32 AF XY: 0.340 AC XY: 25241 AN XY: 74196

Gnomad4 AFR AF: 0.442

Gnomad4 AMR AF: 0.291

Gnomad4 ASJ AF: 0.283

Gnomad4 EAS AF: 0.116

Gnomad4 SAS AF: 0.327

Gnomad4 FIN AF: 0.362

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.335

Alfa AF: 0.309 Hom.: 8575

Bravo AF: 0.337

Asia WGS AF: 0.272 AC: 947 AN: 3478

ClinVar

Significance: association

Submissions summary: Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Lip and oral cavity carcinoma Other:1

association, criteria provided, single submitter

case-control

Department of Biological Science, Sunandan Divatia School of Science, NMIMS University

Jan 01, 2016

The homozygous WT (CC) genotype showed a higher frequency in cases as compared to controls and indicated decreased risk to oral cancer with an OR 0.774 (0.60-0.99). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
Cadd	Benign	0.13
Dann	Benign	0.17

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: rs10090787; hg19: chr8-121810549;