rs7780132

Variant names:

• chr7-85018161-C-T
• rs7780132
• NM_001384900.1:c.1545+91G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 4 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]

SEMA3D Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AD Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001384900.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	NM_001384900.1	MANE Select	c.1545+91G>A		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.1545+91G>A		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.1545+91G>A		intron	N/A	NP_001371831.1	O95025

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.1545+91G>A		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000484038.1	TSL:1	n.671+91G>A		intron	N/A
	SEMA3D	ENST00000916323.1		c.1545+91G>A		intron	N/A	ENSP00000586382.1

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

African (AFR) AF: 0.701 AC: 11297 AN: 16108

American (AMR) AF: 0.497 AC: 16367 AN: 32924

Ashkenazi Jewish (ASJ) AF: 0.595 AC: 11800 AN: 19844

East Asian (EAS) AF: 0.697 AC: 23492 AN: 33722

South Asian (SAS) AF: 0.518 AC: 32115 AN: 61986

European-Finnish (FIN) AF: 0.378 AC: 18992 AN: 50218

Middle Eastern (MID) AF: 0.546 AC: 2033 AN: 3722

European-Non Finnish (NFE) AF: 0.538 AC: 210635 AN: 391768

Other (OTH) AF: 0.560 AC: 18315 AN: 32724

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

African (AFR) AF: 0.702 AC: 29042 AN: 41390

American (AMR) AF: 0.565 AC: 8548 AN: 15142

Ashkenazi Jewish (ASJ) AF: 0.611 AC: 2110 AN: 3456

East Asian (EAS) AF: 0.732 AC: 3739 AN: 5106

South Asian (SAS) AF: 0.527 AC: 2538 AN: 4814

European-Finnish (FIN) AF: 0.376 AC: 3963 AN: 10550

Middle Eastern (MID) AF: 0.620 AC: 181 AN: 292

European-Non Finnish (NFE) AF: 0.531 AC: 35950 AN: 67656

Other (OTH) AF: 0.593 AC: 1251 AN: 2108

Alfa AF: 0.555 Hom.: 36251

Bravo AF: 0.599

Asia WGS AF: 0.640 AC: 2223 AN: 3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	5.8
DANN	Benign	0.46
PhyloP100		1.5
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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs7780132;

hg19: chr7-84647477;