7-85122635-T-C

Variant names:

• chr7-85122635-T-C
• rs2190208
• NM_001384900.1:c.-40-704A>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.-40-704A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.509 in 151,906 control chromosomes in the GnomAD database, including 20,080 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 0.51 (20080 hom., cov: 31)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.259
• 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]

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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.595 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.-40-704A>G		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.-40-704A>G		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.-40-704A>G		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.-40-704A>G		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.-40-704A>G		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.-40-704A>G		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.509 AC: 77271 AN: 151786 Hom.: 20063 Cov.: 31

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.616

Gnomad AMR AF: 0.399

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.613

Gnomad SAS AF: 0.503

Gnomad FIN AF: 0.441

Gnomad MID AF: 0.443

Gnomad NFE AF: 0.488

Gnomad OTH AF: 0.504

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

GnomAD4 genome AF: 0.509 AC: 77335 AN: 151906 Hom.: 20080 Cov.: 31 AF XY: 0.506 AC XY: 37537 AN XY: 74236

African (AFR) AF: 0.593 AC: 24552 AN: 41410

American (AMR) AF: 0.398 AC: 6072 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1582 AN: 3466

East Asian (EAS) AF: 0.612 AC: 3160 AN: 5160

South Asian (SAS) AF: 0.504 AC: 2420 AN: 4806

European-Finnish (FIN) AF: 0.441 AC: 4661 AN: 10562

Middle Eastern (MID) AF: 0.456 AC: 134 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33116 AN: 67938

Other (OTH) AF: 0.509 AC: 1076 AN: 2112

Alfa AF: 0.491 Hom.: 30580

Bravo AF: 0.508

Asia WGS AF: 0.604 AC: 2100 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.3
DANN	Benign	0.64
PhyloP100		-0.26
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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: rs2190208;

hg19: chr7-84751951;