rs7839488

Variant names:

• chr8-120550178-G-A
• rs7839488
• NM_021021.4:c.1137-1220C>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.1137-1220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.469 in 152,032 control chromosomes in the GnomAD database, including 19,207 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 0.47 (19207 hom., cov: 32)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.381
• Publications: 20 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=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.621 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SNTB1	NM_021021.4	c.1137-1220C>T		intron_variant	Intron 4 of 6	ENST00000517992.2	NP_066301.1
SNTB1	XM_047422126.1	c.558-1220C>T		intron_variant	Intron 4 of 6		XP_047278082.1
SNTB1	XM_047422127.1	c.558-1220C>T		intron_variant	Intron 4 of 6		XP_047278083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2	c.1137-1220C>T		intron_variant	Intron 4 of 6	1	NM_021021.4	ENSP00000431124.1
SNTB1	ENST00000395601.7	c.1137-1220C>T		intron_variant	Intron 5 of 7	5		ENSP00000378965.3
SNTB1	ENST00000648490.1	n.*12+953C>T		intron_variant	Intron 5 of 7			ENSP00000497707.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71226 AN: 151914 Hom.: 19208 Cov.: 32

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.465

Gnomad ASJ AF: 0.453

Gnomad EAS AF: 0.240

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.354

Gnomad NFE AF: 0.626

Gnomad OTH AF: 0.501

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

GnomAD4 genome AF: 0.469 AC: 71231 AN: 152032 Hom.: 19207 Cov.: 32 AF XY: 0.464 AC XY: 34477 AN XY: 74326

African (AFR) AF: 0.219 AC: 9085 AN: 41476

American (AMR) AF: 0.465 AC: 7102 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.453 AC: 1571 AN: 3468

East Asian (EAS) AF: 0.241 AC: 1242 AN: 5164

South Asian (SAS) AF: 0.413 AC: 1989 AN: 4818

European-Finnish (FIN) AF: 0.569 AC: 6004 AN: 10554

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

European-Non Finnish (NFE) AF: 0.626 AC: 42529 AN: 67970

Other (OTH) AF: 0.497 AC: 1049 AN: 2110

Alfa AF: 0.571 Hom.: 109150

Bravo AF: 0.453

Asia WGS AF: 0.314 AC: 1090 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.5
DANN	Benign	0.53
PhyloP100		0.38
Mutation Taster		=99/1	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: rs7839488; hg19: chr8-121562418;