8-120556681-C-T

Variant names:

• chr8-120556681-C-T
• rs4395927
• NM_021021.4:c.1137-7723G>A

Variant summary

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

The NM_021021.4(SNTB1):​c.1137-7723G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.428 in 151,992 control chromosomes in the GnomAD database, including 15,581 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 0.43 (15581 hom., cov: 32)
• Consequence: SNTB1 NM_021021.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.243
• Publications: 12 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 = 0.557 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021021.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTB1	NM_021021.4	MANE Select	c.1137-7723G>A		intron	N/A	NP_066301.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SNTB1	ENST00000517992.2	TSL:1 MANE Select	c.1137-7723G>A		intron	N/A	ENSP00000431124.1
	SNTB1	ENST00000395601.7	TSL:5	c.1137-7723G>A		intron	N/A	ENSP00000378965.3
	SNTB1	ENST00000648490.1		n.1137-5430G>A		intron	N/A	ENSP00000497707.1

Frequencies

GnomAD3 genomes AF: 0.428 AC: 64949 AN: 151874 Hom.: 15576 Cov.: 32

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.463

Gnomad AMR AF: 0.412

Gnomad ASJ AF: 0.404

Gnomad EAS AF: 0.251

Gnomad SAS AF: 0.404

Gnomad FIN AF: 0.517

Gnomad MID AF: 0.297

Gnomad NFE AF: 0.561

Gnomad OTH AF: 0.453

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

GnomAD4 genome AF: 0.428 AC: 64989 AN: 151992 Hom.: 15581 Cov.: 32 AF XY: 0.425 AC XY: 31587 AN XY: 74272

African (AFR) AF: 0.217 AC: 8994 AN: 41456

American (AMR) AF: 0.412 AC: 6290 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.404 AC: 1401 AN: 3466

East Asian (EAS) AF: 0.251 AC: 1297 AN: 5166

South Asian (SAS) AF: 0.403 AC: 1944 AN: 4818

European-Finnish (FIN) AF: 0.517 AC: 5451 AN: 10548

Middle Eastern (MID) AF: 0.306 AC: 90 AN: 294

European-Non Finnish (NFE) AF: 0.561 AC: 38151 AN: 67958

Other (OTH) AF: 0.449 AC: 949 AN: 2112

Alfa AF: 0.504 Hom.: 59681

Bravo AF: 0.413

Asia WGS AF: 0.320 AC: 1112 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	6.5
DANN	Benign	0.83
PhyloP100		-0.24
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: rs4395927; hg19: chr8-121568921;