rs7632505

Variant names:

• chr3-123019460-A-G
• rs7632505
• NM_001031702.4:c.-39+8004T>C

Variant summary

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

The NM_001031702.4(SEMA5B):​c.-39+8004T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.329 in 152,092 control chromosomes in the GnomAD database, including 14,178 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 0.33 (14178 hom., cov: 32)
• Consequence: SEMA5B NM_001031702.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.640
• Publications: 8 publications found

Genes affected

SEMA5B (HGNC:10737): (semaphorin 5B) This gene encodes a member of the semaphorin protein family which regulates axon growth during development of the nervous system. The encoded protein has a characteristic Sema domain near the N-terminus, through which semaphorins bind to plexin, and five thrombospondin type 1 repeats in the C-terminal region of the protein. The protein product may be cleaved and exist as a secreted molecule (PMID: 19463192). Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2012]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.768 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001031702.4. 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
	SEMA5B	NM_001031702.4	MANE Select	c.-39+8004T>C		intron	N/A	NP_001026872.2
	SEMA5B	NM_001437563.1		c.-39+8004T>C		intron	N/A	NP_001424492.1
	SEMA5B	NM_001437565.1		c.-39+8004T>C		intron	N/A	NP_001424494.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5B	ENST00000357599.8	TSL:1 MANE Select	c.-39+8004T>C		intron	N/A	ENSP00000350215.3
	SEMA5B	ENST00000648990.1		c.-51+8004T>C		intron	N/A	ENSP00000497595.1
	SEMA5B	ENST00000195173.8	TSL:5	c.-51+8004T>C		intron	N/A	ENSP00000195173.5

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49966 AN: 151974 Hom.: 14121 Cov.: 32

Gnomad AFR AF: 0.775

Gnomad AMI AF: 0.0570

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.210

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.106

Gnomad MID AF: 0.222

Gnomad NFE AF: 0.143

Gnomad OTH AF: 0.289

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

GnomAD4 genome AF: 0.329 AC: 50087 AN: 152092 Hom.: 14178 Cov.: 32 AF XY: 0.324 AC XY: 24067 AN XY: 74362

African (AFR) AF: 0.775 AC: 32145 AN: 41458

American (AMR) AF: 0.221 AC: 3380 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.176 AC: 611 AN: 3466

East Asian (EAS) AF: 0.210 AC: 1084 AN: 5168

South Asian (SAS) AF: 0.272 AC: 1312 AN: 4818

European-Finnish (FIN) AF: 0.106 AC: 1121 AN: 10606

Middle Eastern (MID) AF: 0.228 AC: 67 AN: 294

European-Non Finnish (NFE) AF: 0.143 AC: 9692 AN: 67986

Other (OTH) AF: 0.295 AC: 623 AN: 2112

Alfa AF: 0.246 Hom.: 1073

Bravo AF: 0.357

Asia WGS AF: 0.348 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.7
DANN	Benign	0.31
PhyloP100		-0.64
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7632505; hg19: chr3-122738307;