rs72556351

Variant names:

• chr19-35030875-G-A
• rs72556351
• NM_001037.5:c.40+15G>A

Your query was ambiguous. Multiple possible variants found:

• chr19-35030875-G-A
• chr19-35030875-G-T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS1

The NM_001037.5(SCN1B):​c.40+15G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000907 in 661,624 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0000098 (0 hom.)
• Consequence: SCN1B NM_001037.5 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18
• Publications: 3 publications found

Genes affected

SCN1B (HGNC:10586): (sodium voltage-gated channel beta subunit 1) Voltage-gated sodium channels are heteromeric proteins that function in the generation and propagation of action potentials in muscle and neuronal cells. They are composed of one alpha and two beta subunits, where the alpha subunit provides channel activity and the beta-1 subunit modulates the kinetics of channel inactivation. This gene encodes a sodium channel beta-1 subunit. Mutations in this gene result in generalized epilepsy with febrile seizures plus, Brugada syndrome 5, and defects in cardiac conduction. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Oct 2009]

HPN-AS1 (HGNC:47041): (HPN antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-35030875-G-A is Benign according to our data. Variant chr19-35030875-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 669480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population eas. GnomAdExome4 allele frequency = 0.00000977 (5/511934) while in subpopulation EAS AF = 0.000548 (5/9116). AF 95% confidence interval is 0.000215. There are 0 homozygotes in GnomAdExome4. There are 1 alleles in the male GnomAdExome4 subpopulation. Median coverage is 7. This position passed quality control check.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001037.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	NM_001037.5	MANE Select	c.40+15G>A		intron	N/A	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.40+15G>A		intron	N/A	NP_950238.1	Q07699-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1B	ENST00000262631.11	TSL:1 MANE Select	c.40+15G>A		intron	N/A	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.40+15G>A		intron	N/A	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.40+15G>A		intron	N/A	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes AF: 0.00000668 AC: 1 AN: 149690 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000196

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000977 AC: 5 AN: 511934 Hom.: 0 Cov.: 7 AF XY: 0.00000406 AC XY: 1 AN XY: 246234

African (AFR) AF: 0.00 AC: 0 AN: 10126

American (AMR) AF: 0.00 AC: 0 AN: 3376

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5706

East Asian (EAS) AF: 0.000548 AC: 5 AN: 9116

South Asian (SAS) AF: 0.00 AC: 0 AN: 9792

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 11890

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1304

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 441158

Other (OTH) AF: 0.00 AC: 0 AN: 19466

GnomAD4 genome AF: 0.00000668 AC: 1 AN: 149690 Hom.: 0 Cov.: 31 AF XY: 0.0000137 AC XY: 1 AN XY: 72990

African (AFR) AF: 0.00 AC: 0 AN: 41142

American (AMR) AF: 0.00 AC: 0 AN: 15068

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3438

East Asian (EAS) AF: 0.000196 AC: 1 AN: 5104

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9706

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 314

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 67120

Other (OTH) AF: 0.00 AC: 0 AN: 2064

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Brugada syndrome 5 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	10
DANN	Benign	0.80
PhyloP100		1.2
PromoterAI		-0.076	Neutral

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: rs72556351; hg19: chr19-35521779;