rs4455882

chr8-120571043-A-Gchr8-120571043-A-T

Variant summary

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

The NM_021021.4(SNTB1):c.1136+4043T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.561 in 439,396 control chromosomes in the GnomAD database, including 74,923 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 0.46 (18596 hom., cov: 32)
  • Exomes 𝑓: 0.61 (56327 hom.)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0750

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=-0.66).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SNTB1	NM_021021.4	c.1136+4043T>C		intron_variant		ENST00000517992.2
SNTB1	XM_047422126.1	c.557+4043T>C		intron_variant
SNTB1	XM_047422127.1	c.557+4043T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SNTB1	ENST00000517992.2	c.1136+4043T>C		intron_variant		1	NM_021021.4	P1
SNTB1	ENST00000519177.5	n.1178T>C		non_coding_transcript_exon_variant	5/5	1
SNTB1	ENST00000395601.7	c.1136+4043T>C		intron_variant		5		P1
SNTB1	ENST00000648490.1	c.1136+4043T>C		intron_variant, NMD_transcript_variant

Frequencies

GnomAD3 genomes AF: 0.461 AC: 70070 AN: 151954 Hom.: 18591 Cov.: 32

Gnomad AFR AF: 0.205

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.449

Gnomad ASJ AF: 0.483

Gnomad EAS AF: 0.248

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.616

Gnomad OTH AF: 0.493

GnomAD4 exome AF: 0.614 AC: 176519 AN: 287324 Hom.: 56327 Cov.: 5 AF XY: 0.607 AC XY: 88133 AN XY: 145152

Gnomad4 AFR exome AF: 0.210

Gnomad4 AMR exome AF: 0.472

Gnomad4 ASJ exome AF: 0.528

Gnomad4 EAS exome AF: 0.232

Gnomad4 SAS exome AF: 0.455

Gnomad4 FIN exome AF: 0.608

Gnomad4 NFE exome AF: 0.665

Gnomad4 OTH exome AF: 0.574

GnomAD4 genome AF: 0.461 AC: 70105 AN: 152072 Hom.: 18596 Cov.: 32 AF XY: 0.458 AC XY: 34047 AN XY: 74322

Gnomad4 AFR AF: 0.205

Gnomad4 AMR AF: 0.449

Gnomad4 ASJ AF: 0.483

Gnomad4 EAS AF: 0.249

Gnomad4 SAS AF: 0.421

Gnomad4 FIN AF: 0.584

Gnomad4 NFE AF: 0.616

Gnomad4 OTH AF: 0.489

Alfa AF: 0.522 Hom.: 9514

Bravo AF: 0.443

Asia WGS AF: 0.327 AC: 1136 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.5
Dann	Benign	0.91

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: rs4455882; hg19: chr8-121583283;