rs6469937

Variant names:

• chr8-120598198-G-A
• rs6469937
• NM_021021.4:c.997-22973C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021021.4(SNTB1):​c.997-22973C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,880 control chromosomes in the GnomAD database, including 19,933 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 0.48 (19933 hom., cov: 31)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.691
• Publications: 18 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.639 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB1	NM_021021.4	c.997-22973C>T		intron_variant	Intron 3 of 6	ENST00000517992.2	NP_066301.1
SNTB1	XM_011517239.3	c.997-22973C>T		intron_variant	Intron 3 of 4		XP_011515541.1
SNTB1	XM_047422126.1	c.418-22973C>T		intron_variant	Intron 3 of 6		XP_047278082.1
SNTB1	XM_047422127.1	c.418-22973C>T		intron_variant	Intron 3 of 6		XP_047278083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2	c.997-22973C>T		intron_variant	Intron 3 of 6	1	NM_021021.4	ENSP00000431124.1
SNTB1	ENST00000519177.5	n.717-22973C>T		intron_variant	Intron 3 of 4	1
SNTB1	ENST00000395601.7	c.997-22973C>T		intron_variant	Intron 4 of 7	5		ENSP00000378965.3
SNTB1	ENST00000648490.1	n.997-22973C>T		intron_variant	Intron 3 of 7			ENSP00000497707.1

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72839 AN: 151762 Hom.: 19934 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.682

Gnomad AMR AF: 0.461

Gnomad ASJ AF: 0.479

Gnomad EAS AF: 0.260

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.570

Gnomad MID AF: 0.351

Gnomad NFE AF: 0.644

Gnomad OTH AF: 0.500

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

GnomAD4 genome AF: 0.480 AC: 72856 AN: 151880 Hom.: 19933 Cov.: 31 AF XY: 0.475 AC XY: 35236 AN XY: 74204

African (AFR) AF: 0.223 AC: 9219 AN: 41424

American (AMR) AF: 0.461 AC: 7030 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.479 AC: 1660 AN: 3464

East Asian (EAS) AF: 0.260 AC: 1338 AN: 5148

South Asian (SAS) AF: 0.433 AC: 2075 AN: 4796

European-Finnish (FIN) AF: 0.570 AC: 6005 AN: 10538

Middle Eastern (MID) AF: 0.361 AC: 106 AN: 294

European-Non Finnish (NFE) AF: 0.644 AC: 43751 AN: 67944

Other (OTH) AF: 0.497 AC: 1050 AN: 2114

Alfa AF: 0.522 Hom.: 22057

Bravo AF: 0.463

Asia WGS AF: 0.336 AC: 1167 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	5.1
DANN	Benign	0.73
PhyloP100		0.69
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: rs6469937; hg19: chr8-121610438;