rs1555696837

Variant names:

• chr19-4543629-GC-G
• rs1555696837
• NM_032108.4:c.2638delG

Your query was ambiguous. Multiple possible variants found:

• chr19-4543629-GC-G
• chr19-4543629-GC-GCC

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 4P and 4B. PVS1_Moderate PM2 BS2

The NM_032108.4(SEMA6B):​c.2638delG​(p.Ala880ArgfsTer92) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000463 in 1,080,304 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000046 (0 hom.)
• Consequence: SEMA6B NM_032108.4 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.128

Genes affected

SEMA6B (HGNC:10739): (semaphorin 6B) This gene encodes a member of the semaphorin family, a group of proteins characterized by the presence of a conserved semaphorin (sema) domain. Whereas some semaphorins are transmembrane proteins, others are secreted. Semaphorins play a major role in axon guidance. The protein encoded by this gene may be involved in both peripheral and central nervous system development. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PVS1: Loss of function variant, product does not undergo nonsense mediated mRNA decay. Variant is located in the 3'-most exon, not predicted to undergo nonsense mediated mRNA decay. Fraction of 0.0109 CDS is truncated, and there are 0 pathogenic variants in the truncated region.
• PM2: Very rare variant in population databases, with high coverage
• BS2: High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA6B	NM_032108.4	c.2638delG	p.Ala880ArgfsTer92	frameshift_variant	Exon 17 of 17	ENST00000586582.6	NP_115484.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA6B	ENST00000586582.6	c.2638delG	p.Ala880ArgfsTer92	frameshift_variant	Exon 17 of 17	1	NM_032108.4	ENSP00000467290.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000463 AC: 5 AN: 1080304 Hom.: 0 Cov.: 32 AF XY: 0.00000392 AC XY: 2 AN XY: 510400

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000544

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs1555696837; hg19: chr19-4543641;