3-50274469-C-T

Variant names:

• chr3-50274469-C-T
• rs2071203
• NM_001290060.2:c.1244C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001290060.2(SEMA3B):​c.1244C>T​(p.Thr415Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0409 in 1,550,080 control chromosomes in the GnomAD database, including 11,737 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T415S) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.10 (2246 hom., cov: 33)
  • Exomes 𝑓: 0.034 (9491 hom.)
• Consequence: SEMA3B NM_001290060.2 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 1.85
• Publications: 21 publications found

Genes affected

SEMA3B (HGNC:10724): (semaphorin 3B) The protein encoded by this gene belongs to the class-3 semaphorin/collapsin family, whose members function in growth cone guidance during neuronal development. This family member inhibits axonal extension and has been shown to act as a tumor suppressor by inducing apoptosis. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2014]

SEMA3B-AS1 (HGNC:49096): (SEMA3B antisense RNA 1 (head to head))

ACMG classification

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

• BP4: Computational evidence support a benign effect (MetaRNN=1.2084379E-5).
• BP6: Variant 3-50274469-C-T is Benign according to our data. Variant chr3-50274469-C-T is described in ClinVar as Benign. ClinVar VariationId is 3058923.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290060.2. 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
	SEMA3B	NM_001290060.2	MANE Select	c.1244C>T	p.Thr415Ile	missense	Exon 11 of 17	NP_001276989.1	Q13214-1
	SEMA3B	NM_001290061.1		c.1259C>T	p.Thr420Ile	missense	Exon 11 of 17	NP_001276990.1	Q13214
	SEMA3B	NM_001435956.1		c.1244C>T	p.Thr415Ile	missense	Exon 14 of 20	NP_001422885.1	Q13214-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3B	ENST00000616701.5	TSL:1 MANE Select	c.1244C>T	p.Thr415Ile	missense	Exon 11 of 17	ENSP00000484146.1	Q13214-1
	SEMA3B	ENST00000611067.4	TSL:1	c.1259C>T	p.Thr420Ile	missense	Exon 11 of 17	ENSP00000480680.1	A0A0C4DGV8
	SEMA3B	ENST00000433753.4	TSL:1	c.1241C>T	p.Thr414Ile	missense	Exon 11 of 17	ENSP00000485281.1	Q13214-2

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15665 AN: 152076 Hom.: 2244 Cov.: 33

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.266

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.597

Gnomad SAS AF: 0.0207

Gnomad FIN AF: 0.0467

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00359

Gnomad OTH AF: 0.0856

GnomAD2 exomes AF: 0.121 AC: 24003 AN: 197684 AF XY: 0.101

Gnomad AFR exome AF: 0.178

Gnomad AMR exome AF: 0.415

Gnomad ASJ exome AF: 0.00418

Gnomad EAS exome AF: 0.610

Gnomad FIN exome AF: 0.0448

Gnomad NFE exome AF: 0.00385

Gnomad OTH exome AF: 0.0651

GnomAD4 exome AF: 0.0341 AC: 47692 AN: 1397886 Hom.: 9491 Cov.: 31 AF XY: 0.0314 AC XY: 21698 AN XY: 690496

African (AFR) AF: 0.195 AC: 6068 AN: 31128

American (AMR) AF: 0.384 AC: 12859 AN: 33456

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 102 AN: 22104

East Asian (EAS) AF: 0.534 AC: 20585 AN: 38568

South Asian (SAS) AF: 0.00997 AC: 751 AN: 75314

European-Finnish (FIN) AF: 0.0440 AC: 2267 AN: 51520

Middle Eastern (MID) AF: 0.00770 AC: 42 AN: 5452

European-Non Finnish (NFE) AF: 0.00167 AC: 1811 AN: 1082780

Other (OTH) AF: 0.0557 AC: 3207 AN: 57564

GnomAD4 genome AF: 0.103 AC: 15693 AN: 152194 Hom.: 2246 Cov.: 33 AF XY: 0.110 AC XY: 8156 AN XY: 74398

African (AFR) AF: 0.181 AC: 7499 AN: 41482

American (AMR) AF: 0.266 AC: 4071 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.597 AC: 3084 AN: 5162

South Asian (SAS) AF: 0.0205 AC: 99 AN: 4828

European-Finnish (FIN) AF: 0.0467 AC: 496 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.00359 AC: 244 AN: 68024

Other (OTH) AF: 0.0862 AC: 182 AN: 2112

Alfa AF: 0.0515 Hom.: 2547

Bravo AF: 0.129

TwinsUK AF: 0.000539 AC: 2

ALSPAC AF: 0.00234 AC: 9

ESP6500AA AF: 0.170 AC: 653

ESP6500EA AF: 0.00509 AC: 42

ExAC AF: 0.106 AC: 12791

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3B-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.049
BayesDel_addAF	Uncertain	0.047	T
BayesDel_noAF	Pathogenic	0.44
CADD	Benign	15
DANN	Benign	0.94
DEOGEN2	Benign	0.024	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.0
FATHMM_MKL	Benign	0.019	N
LIST_S2	Benign	0.068	T
MetaRNN	Benign	0.000012	T
MetaSVM	Benign	-0.91	T
PhyloP100		1.8
PrimateAI	Benign	0.24	T
Sift4G	Benign	0.70	T
Polyphen		0.0	B
Vest4		0.015
ClinPred		0.0062	T
GERP RS		3.4
Varity_R		0.042
gMVP		0.096

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs2071203; hg19: chr3-50311900; COSMIC: COSV57114262; COSMIC: COSV57114262;