rs17559084

chr7-85015184-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_001384900.1(SEMA3D):c.1578G>A(p.Leu526=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,609,492 control chromosomes in the GnomAD database, including 76,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4880 hom., cov: 32)
  • Exomes 𝑓: 0.30 (71253 hom.)
• Consequence: SEMA3D NM_001384900.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.516

Genes affected

SEMA3D (HGNC:10726): (semaphorin 3D) This gene encodes a member of the semaphorin III family of secreted signaling proteins that are involved in axon guidance during neuronal development. The encoded protein contains an N-terminal Sema domain, an immunoglobulin like domain and a C-terminal basic domain. The protein encoded by this gene binds neuropilin and plays an important role in cardiovascular development. [provided by RefSeq, Aug 2016]

ACMG classification

Verdict is Benign. Variant got -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-85015184-C-T is Benign according to our data. Variant chr7-85015184-C-T is described in ClinVar as [Benign]. Clinvar id is 3060649.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3D	NM_001384900.1	c.1578G>A	p.Leu526=	synonymous_variant	16/19	ENST00000284136.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3D	ENST00000284136.11	c.1578G>A	p.Leu526=	synonymous_variant	16/19	5	NM_001384900.1	P1
SEMA3D	ENST00000484038.1	n.704G>A		non_coding_transcript_exon_variant	7/10	1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34977 AN: 151626 Hom.: 4883 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.255

GnomAD3 exomes AF: 0.242 AC: 60343 AN: 249844 Hom.: 8633 AF XY: 0.250 AC XY: 33821 AN XY: 135022

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.0625

Gnomad SAS exome AF: 0.196

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.303 AC: 441624 AN: 1457750 Hom.: 71253 Cov.: 34 AF XY: 0.301 AC XY: 218397 AN XY: 725132

Gnomad4 AFR exome AF: 0.0764

Gnomad4 AMR exome AF: 0.156

Gnomad4 ASJ exome AF: 0.294

Gnomad4 EAS exome AF: 0.0540

Gnomad4 SAS exome AF: 0.197

Gnomad4 FIN exome AF: 0.237

Gnomad4 NFE exome AF: 0.338

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.230 AC: 34968 AN: 151742 Hom.: 4880 Cov.: 32 AF XY: 0.225 AC XY: 16704 AN XY: 74140

Gnomad4 AFR AF: 0.0854

Gnomad4 AMR AF: 0.221

Gnomad4 ASJ AF: 0.308

Gnomad4 EAS AF: 0.0632

Gnomad4 SAS AF: 0.187

Gnomad4 FIN AF: 0.230

Gnomad4 NFE AF: 0.330

Gnomad4 OTH AF: 0.253

Alfa AF: 0.307 Hom.: 12277

Bravo AF: 0.221

Asia WGS AF: 0.118 AC: 413 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.329

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

SEMA3D-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 19, 2022

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
Cadd	Benign	9.0
Dann	Benign	0.87

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17559084; hg19: chr7-84644500; COSMIC: COSV52393702;