rs993312

Positions:

• chr7-85118528-C-A
• chr7-85118528-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384900.1(SEMA3D):​c.151+3213G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.227 in 151,984 control chromosomes in the GnomAD database, including 4,234 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 0.23 (4234 hom., cov: 32)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.667

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.374 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3D	NM_001384900.1	c.151+3213G>T		intron_variant		ENST00000284136.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3D	ENST00000284136.11	c.151+3213G>T		intron_variant		5	NM_001384900.1	P1
SEMA3D	ENST00000444867.1	c.151+3213G>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.227 AC: 34514 AN: 151866 Hom.: 4238 Cov.: 32

Gnomad AFR AF: 0.165

Gnomad AMI AF: 0.431

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.291

Gnomad EAS AF: 0.388

Gnomad SAS AF: 0.332

Gnomad FIN AF: 0.207

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.249

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

GnomAD4 genome AF: 0.227 AC: 34529 AN: 151984 Hom.: 4234 Cov.: 32 AF XY: 0.227 AC XY: 16894 AN XY: 74268

Gnomad4 AFR AF: 0.165

Gnomad4 AMR AF: 0.195

Gnomad4 ASJ AF: 0.291

Gnomad4 EAS AF: 0.388

Gnomad4 SAS AF: 0.332

Gnomad4 FIN AF: 0.207

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.249

Alfa AF: 0.244 Hom.: 2365

Bravo AF: 0.222

Asia WGS AF: 0.352 AC: 1224 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	2.5
DANN	Benign	0.50

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: rs993312; hg19: chr7-84747844;