NM_021021.4:c.571+12964G>A

Variant names:

• chr8-120798309-C-T
• rs10090787
• NM_021021.4:c.571+12964G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 publications found

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

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
SNTB1	NM_021021.4	c.571+12964G>A		intron_variant	Intron 1 of 6	ENST00000517992.2	NP_066301.1
SNTB1	XM_011517239.3	c.571+12964G>A		intron_variant	Intron 1 of 4		XP_011515541.1
SNTB1	XM_047422126.1	c.-9+4475G>A		intron_variant	Intron 1 of 6		XP_047278082.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2	c.571+12964G>A		intron_variant	Intron 1 of 6	1	NM_021021.4	ENSP00000431124.1
SNTB1	ENST00000519177.5	n.291+12964G>A		intron_variant	Intron 1 of 4	1
SNTB1	ENST00000395601.7	c.571+12964G>A		intron_variant	Intron 2 of 7	5		ENSP00000378965.3
SNTB1	ENST00000648490.1	n.571+12964G>A		intron_variant	Intron 1 of 7			ENSP00000497707.1

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

African (AFR) AF: 0.442 AC: 18292 AN: 41356

American (AMR) AF: 0.291 AC: 4433 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.283 AC: 983 AN: 3468

East Asian (EAS) AF: 0.116 AC: 597 AN: 5152

South Asian (SAS) AF: 0.327 AC: 1574 AN: 4818

European-Finnish (FIN) AF: 0.362 AC: 3827 AN: 10586

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20646 AN: 67878

Other (OTH) AF: 0.335 AC: 702 AN: 2096

Alfa AF: 0.320 Hom.: 14415

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

Jan 01, 2016

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

Significance: association

Review Status: criteria provided, single submitter

Collection Method: case-control

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
PhyloP100		-1.3
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10090787; hg19: chr8-121810549;