rs7780132

Positions:

• chr7-85018161-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.1545+91G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.545 in 794,442 control chromosomes in the GnomAD database, including 120,812 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 0.58 (26333 hom., cov: 32)
  • Exomes 𝑓: 0.54 (94479 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.50

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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.713 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.1545+91G>A		intron_variant		ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.1545+91G>A		intron_variant		5	NM_001384900.1	ENSP00000284136	P1
SEMA3D	ENST00000484038.1	n.671+91G>A		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.580 AC: 87788 AN: 151308 Hom.: 26278 Cov.: 32

Gnomad AFR AF: 0.701

Gnomad AMI AF: 0.639

Gnomad AMR AF: 0.564

Gnomad ASJ AF: 0.611

Gnomad EAS AF: 0.733

Gnomad SAS AF: 0.526

Gnomad FIN AF: 0.376

Gnomad MID AF: 0.602

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.592

GnomAD4 exome AF: 0.537 AC: 345046 AN: 643016 Hom.: 94479 AF XY: 0.535 AC XY: 183965 AN XY: 343722

Gnomad4 AFR exome AF: 0.701

Gnomad4 AMR exome AF: 0.497

Gnomad4 ASJ exome AF: 0.595

Gnomad4 EAS exome AF: 0.697

Gnomad4 SAS exome AF: 0.518

Gnomad4 FIN exome AF: 0.378

Gnomad4 NFE exome AF: 0.538

Gnomad4 OTH exome AF: 0.560

GnomAD4 genome AF: 0.581 AC: 87905 AN: 151426 Hom.: 26333 Cov.: 32 AF XY: 0.574 AC XY: 42437 AN XY: 73960

Gnomad4 AFR AF: 0.702

Gnomad4 AMR AF: 0.565

Gnomad4 ASJ AF: 0.611

Gnomad4 EAS AF: 0.732

Gnomad4 SAS AF: 0.527

Gnomad4 FIN AF: 0.376

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.593

Alfa AF: 0.542 Hom.: 4704

Bravo AF: 0.599

Asia WGS AF: 0.640 AC: 2223 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.46

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: rs7780132; hg19: chr7-84647477;