3-122961294-A-G

Variant names:

• chr3-122961294-A-G
• rs13094003
• NM_001031702.4:c.-31T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001256347.1(SEMA5B):​c.132T>C​(p.Gly44Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.225 in 1,612,324 control chromosomes in the GnomAD database, including 42,009 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 0.24 (4382 hom., cov: 32)
  • Exomes 𝑓: 0.22 (37627 hom.)
• Consequence: SEMA5B NM_001256347.1 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0260
• Publications: 13 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]

ENSG00000306095 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP7: Synonymous conserved (PhyloP=-0.026 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001256347.1. 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
	SEMA5B	NM_001031702.4	MANE Select	c.-31T>C		5_prime_UTR	Exon 2 of 23	NP_001026872.2	Q9P283-1
	SEMA5B	NM_001256347.1		c.132T>C	p.Gly44Gly	synonymous	Exon 2 of 23	NP_001243276.1	Q9P283-4
	SEMA5B	NM_001437563.1		c.-31T>C		5_prime_UTR	Exon 2 of 23	NP_001424492.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5B	ENST00000357599.8	TSL:1 MANE Select	c.-31T>C		5_prime_UTR	Exon 2 of 23	ENSP00000350215.3	Q9P283-1
	SEMA5B	ENST00000451055.6	TSL:2	c.132T>C	p.Gly44Gly	synonymous	Exon 2 of 23	ENSP00000389588.2	Q9P283-4
	SEMA5B	ENST00000616742.4	TSL:5	c.-31T>C		5_prime_UTR	Exon 2 of 23	ENSP00000479602.1	Q9P283-1

Frequencies

GnomAD3 genomes AF: 0.236 AC: 35925 AN: 151974 Hom.: 4376 Cov.: 32

Gnomad AFR AF: 0.238

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.262

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.373

Gnomad SAS AF: 0.208

Gnomad FIN AF: 0.288

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.212

Gnomad OTH AF: 0.234

GnomAD2 exomes AF: 0.244 AC: 60934 AN: 249638 AF XY: 0.239

Gnomad AFR exome AF: 0.241

Gnomad AMR exome AF: 0.283

Gnomad ASJ exome AF: 0.276

Gnomad EAS exome AF: 0.389

Gnomad FIN exome AF: 0.282

Gnomad NFE exome AF: 0.211

Gnomad OTH exome AF: 0.239

GnomAD4 exome AF: 0.224 AC: 327562 AN: 1460232 Hom.: 37627 Cov.: 33 AF XY: 0.223 AC XY: 162167 AN XY: 726428

African (AFR) AF: 0.240 AC: 8005 AN: 33420

American (AMR) AF: 0.285 AC: 12686 AN: 44572

Ashkenazi Jewish (ASJ) AF: 0.282 AC: 7339 AN: 26046

East Asian (EAS) AF: 0.393 AC: 15588 AN: 39668

South Asian (SAS) AF: 0.198 AC: 17009 AN: 86098

European-Finnish (FIN) AF: 0.277 AC: 14785 AN: 53376

Middle Eastern (MID) AF: 0.212 AC: 1219 AN: 5756

European-Non Finnish (NFE) AF: 0.213 AC: 236708 AN: 1110990

Other (OTH) AF: 0.236 AC: 14223 AN: 60306

GnomAD4 genome AF: 0.236 AC: 35949 AN: 152092 Hom.: 4382 Cov.: 32 AF XY: 0.243 AC XY: 18035 AN XY: 74330

African (AFR) AF: 0.238 AC: 9884 AN: 41482

American (AMR) AF: 0.262 AC: 4005 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.291 AC: 1012 AN: 3472

East Asian (EAS) AF: 0.373 AC: 1927 AN: 5162

South Asian (SAS) AF: 0.207 AC: 997 AN: 4810

European-Finnish (FIN) AF: 0.288 AC: 3048 AN: 10580

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.212 AC: 14391 AN: 67968

Other (OTH) AF: 0.233 AC: 492 AN: 2114

Alfa AF: 0.222 Hom.: 15566

Bravo AF: 0.238

Asia WGS AF: 0.244 AC: 848 AN: 3478

EpiCase AF: 0.213

EpiControl AF: 0.212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.2
DANN	Benign	0.66
PhyloP100		-0.026
Mutation Taster		=300/0	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: rs13094003; hg19: chr3-122680141; COSMIC: COSV52091520;