rs4512418

Variant names:

• chr8-120674515-T-C
• rs4512418
• NM_021021.4:c.788+19177A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 2 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.361 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.788+19177A>G		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.788+19177A>G		intron	N/A	ENSP00000431124.1
	SNTB1	ENST00000519177.5	TSL:1	n.508+19177A>G		intron	N/A
	SNTB1	ENST00000395601.7	TSL:5	c.788+19177A>G		intron	N/A	ENSP00000378965.3

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

African (AFR) AF: 0.110 AC: 4565 AN: 41546

American (AMR) AF: 0.370 AC: 5648 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.433 AC: 1502 AN: 3468

East Asian (EAS) AF: 0.289 AC: 1497 AN: 5178

South Asian (SAS) AF: 0.310 AC: 1496 AN: 4830

European-Finnish (FIN) AF: 0.325 AC: 3444 AN: 10582

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.365 AC: 24827 AN: 67992

Other (OTH) AF: 0.330 AC: 697 AN: 2114

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 v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.0050
DANN	Benign	0.44
PhyloP100		-2.9
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: rs4512418; hg19: chr8-121686755;