rs4512418

Positions:

• chr8-120674515-T-C

Variant summary

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

The NM_021021.4(SNTB1):​c.788+19177A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.29 in 152,198 control chromosomes in the GnomAD database, including 7,443 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 0.29 (7443 hom., cov: 33)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.92

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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SNTB1	NM_021021.4	c.788+19177A>G		intron_variant		ENST00000517992.2	NP_066301.1
SNTB1	XM_011517239.3	c.788+19177A>G		intron_variant			XP_011515541.1
SNTB1	XM_047422126.1	c.209+19177A>G		intron_variant			XP_047278082.1
SNTB1	XM_047422127.1	c.209+19177A>G		intron_variant			XP_047278083.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SNTB1	ENST00000517992.2	c.788+19177A>G		intron_variant		1	NM_021021.4	ENSP00000431124	P1

Frequencies

GnomAD3 genomes AF: 0.290 AC: 44142 AN: 152080 Hom.: 7440 Cov.: 33

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.416

Gnomad AMR AF: 0.369

Gnomad ASJ AF: 0.433

Gnomad EAS AF: 0.288

Gnomad SAS AF: 0.311

Gnomad FIN AF: 0.325

Gnomad MID AF: 0.342

Gnomad NFE AF: 0.365

Gnomad OTH AF: 0.326

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

GnomAD4 genome AF: 0.290 AC: 44153 AN: 152198 Hom.: 7443 Cov.: 33 AF XY: 0.289 AC XY: 21531 AN XY: 74392

Gnomad4 AFR AF: 0.110

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.433

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.310

Gnomad4 FIN AF: 0.325

Gnomad4 NFE AF: 0.365

Gnomad4 OTH AF: 0.330

Alfa AF: 0.315 Hom.: 1339

Bravo AF: 0.287

Asia WGS AF: 0.312 AC: 1085 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.44

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: rs4512418; hg19: chr8-121686755;