19-35030875-G-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001037.5(SCN1B):​c.40+15G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.204 in 659,806 control chromosomes in the GnomAD database, including 14,317 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.19 (2955 hom., cov: 31)
  • Exomes 𝑓: 0.21 (11362 hom.)
• Consequence: SCN1B NM_001037.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 19-35030875-G-T is Benign according to our data. Variant chr19-35030875-G-T is described in ClinVar as Benign. ClinVar VariationId is 93481.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

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>T		intron	N/A	NP_001028.1	Q07699-1
	SCN1B	NM_199037.5		c.40+15G>T		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>T		intron	N/A	ENSP00000262631.3	Q07699-1
	SCN1B	ENST00000415950.5	TSL:1	c.40+15G>T		intron	N/A	ENSP00000396915.2	Q07699-2
	SCN1B	ENST00000638536.1	TSL:1	c.40+15G>T		intron	N/A	ENSP00000492022.1	Q07699-1

Frequencies

GnomAD3 genomes AF: 0.195 AC: 29144 AN: 149626 Hom.: 2956 Cov.: 31

Gnomad AFR AF: 0.188

Gnomad AMI AF: 0.273

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.222

Gnomad EAS AF: 0.0507

Gnomad SAS AF: 0.0849

Gnomad FIN AF: 0.205

Gnomad MID AF: 0.271

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.217

GnomAD2 exomes AF: 0.310 AC: 18 AN: 58 AF XY: 0.321

Gnomad ASJ exome AF: 0.500

Gnomad NFE exome AF: 0.296

GnomAD4 exome AF: 0.207 AC: 105364 AN: 510072 Hom.: 11362 Cov.: 7 AF XY: 0.207 AC XY: 50782 AN XY: 245356

African (AFR) AF: 0.199 AC: 2009 AN: 10090

American (AMR) AF: 0.249 AC: 838 AN: 3372

Ashkenazi Jewish (ASJ) AF: 0.236 AC: 1344 AN: 5690

East Asian (EAS) AF: 0.105 AC: 959 AN: 9112

South Asian (SAS) AF: 0.0866 AC: 846 AN: 9772

European-Finnish (FIN) AF: 0.247 AC: 2932 AN: 11884

Middle Eastern (MID) AF: 0.284 AC: 368 AN: 1296

European-Non Finnish (NFE) AF: 0.210 AC: 92111 AN: 439444

Other (OTH) AF: 0.204 AC: 3957 AN: 19412

GnomAD4 genome AF: 0.195 AC: 29152 AN: 149734 Hom.: 2955 Cov.: 31 AF XY: 0.193 AC XY: 14099 AN XY: 73068

African (AFR) AF: 0.188 AC: 7737 AN: 41236

American (AMR) AF: 0.216 AC: 3263 AN: 15082

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 763 AN: 3436

East Asian (EAS) AF: 0.0505 AC: 257 AN: 5088

South Asian (SAS) AF: 0.0844 AC: 407 AN: 4824

European-Finnish (FIN) AF: 0.205 AC: 1992 AN: 9696

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.208 AC: 13950 AN: 67088

Other (OTH) AF: 0.217 AC: 453 AN: 2086

Alfa AF: 0.208 Hom.: 404

Bravo AF: 0.195

Asia WGS AF: 0.105 AC: 337 AN: 3200

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	7	not specified (7)
-	-	2	Brugada syndrome 5 (2)
-	-	1	Generalized epilepsy with febrile seizures plus, type 1 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.5
DANN	Benign	0.42
PhyloP100		1.2
PromoterAI		-0.087	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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;