rs2240394

Variant names:

• chr7-85063625-T-C
• rs2240394
• NM_001384900.1:c.718+1799A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001384900.1(SEMA3D):​c.718+1799A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,160 control chromosomes in the GnomAD database, including 2,305 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 0.16 (2305 hom., cov: 32)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.123
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.25 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.718+1799A>G		intron_variant	Intron 8 of 18	ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.718+1799A>G		intron_variant	Intron 8 of 18	5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000444867.1	c.718+1799A>G		intron_variant	Intron 8 of 9	1		ENSP00000401366.1

Frequencies

GnomAD3 genomes AF: 0.164 AC: 24932 AN: 152042 Hom.: 2306 Cov.: 32

Gnomad AFR AF: 0.254

Gnomad AMI AF: 0.0943

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.0977

Gnomad EAS AF: 0.184

Gnomad SAS AF: 0.0319

Gnomad FIN AF: 0.110

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.138

Gnomad OTH AF: 0.153

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

GnomAD4 genome AF: 0.164 AC: 24943 AN: 152160 Hom.: 2305 Cov.: 32 AF XY: 0.162 AC XY: 12037 AN XY: 74410

African (AFR) AF: 0.254 AC: 10534 AN: 41490

American (AMR) AF: 0.128 AC: 1961 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.0977 AC: 339 AN: 3470

East Asian (EAS) AF: 0.184 AC: 953 AN: 5176

South Asian (SAS) AF: 0.0315 AC: 152 AN: 4822

European-Finnish (FIN) AF: 0.110 AC: 1170 AN: 10596

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.138 AC: 9403 AN: 68012

Other (OTH) AF: 0.152 AC: 321 AN: 2116

Alfa AF: 0.142 Hom.: 6963

Bravo AF: 0.171

Asia WGS AF: 0.0970 AC: 339 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.48
DANN	Benign	0.66
PhyloP100		-0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2240394; hg19: chr7-84692941;