rs10486848

chr7-85108367-G-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The NM_001384900.1(SEMA3D):c.152-10402C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,952 control chromosomes in the GnomAD database, including 1,707 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 0.13 (1707 hom., cov: 32)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.457

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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.45).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.196 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA3D	NM_001384900.1	c.152-10402C>T		intron_variant		ENST00000284136.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA3D	ENST00000284136.11	c.152-10402C>T		intron_variant		5	NM_001384900.1	P1
SEMA3D	ENST00000444867.1	c.152-10402C>T		intron_variant		1

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20356 AN: 151834 Hom.: 1705 Cov.: 32

Gnomad AFR AF: 0.0428

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.127

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.00135

Gnomad SAS AF: 0.0651

Gnomad FIN AF: 0.181

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.198

Gnomad OTH AF: 0.143

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

GnomAD4 genome AF: 0.134 AC: 20350 AN: 151952 Hom.: 1707 Cov.: 32 AF XY: 0.132 AC XY: 9771 AN XY: 74270

Gnomad4 AFR AF: 0.0427

Gnomad4 AMR AF: 0.126

Gnomad4 ASJ AF: 0.132

Gnomad4 EAS AF: 0.00136

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.181

Gnomad4 NFE AF: 0.198

Gnomad4 OTH AF: 0.141

Alfa AF: 0.174 Hom.: 3387

Bravo AF: 0.126

Asia WGS AF: 0.0320 AC: 115 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	10
Dann	Benign	0.74

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: rs10486848; hg19: chr7-84737683;