rs7839488

chr8-120550178-G-A

Variant summary

Our verdict is Benign. Variant got -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

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=-0.8).
• 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/exons	MANE	UniProt
SNTB1	NM_021021.4	c.1137-1220C>T		intron_variant		ENST00000517992.2
SNTB1	XM_047422126.1	c.558-1220C>T		intron_variant
SNTB1	XM_047422127.1	c.558-1220C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTB1	ENST00000517992.2	c.1137-1220C>T		intron_variant		1	NM_021021.4	P1
SNTB1	ENST00000395601.7	c.1137-1220C>T		intron_variant		5		P1
SNTB1	ENST00000648490.1	c.*12+953C>T		intron_variant, NMD_transcript_variant

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

Gnomad4 AFR AF: 0.219

Gnomad4 AMR AF: 0.465

Gnomad4 ASJ AF: 0.453

Gnomad4 EAS AF: 0.241

Gnomad4 SAS AF: 0.413

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.626

Gnomad4 OTH AF: 0.497

Alfa AF: 0.590 Hom.: 53250

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

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: rs7839488; hg19: chr8-121562418;