7-85070071-T-C

Variant names:

• chr7-85070071-T-C
• rs6966472
• NM_001384900.1:c.496-1787A>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.496-1787A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 152,170 control chromosomes in the GnomAD database, including 3,129 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 0.18 (3129 hom., cov: 32)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• 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=-0.59).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.317 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.496-1787A>G		intron	N/A	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.496-1787A>G		intron	N/A	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.496-1787A>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.496-1787A>G		intron	N/A	ENSP00000284136.6	O95025
	SEMA3D	ENST00000444867.1	TSL:1	c.496-1787A>G		intron	N/A	ENSP00000401366.1	C9JYT6
	SEMA3D	ENST00000916323.1		c.496-1787A>G		intron	N/A	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.184 AC: 27919 AN: 152052 Hom.: 3128 Cov.: 32

Gnomad AFR AF: 0.322

Gnomad AMI AF: 0.0868

Gnomad AMR AF: 0.136

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.187

Gnomad SAS AF: 0.0308

Gnomad FIN AF: 0.109

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.166

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

GnomAD4 genome AF: 0.184 AC: 27943 AN: 152170 Hom.: 3129 Cov.: 32 AF XY: 0.180 AC XY: 13404 AN XY: 74406

African (AFR) AF: 0.322 AC: 13346 AN: 41474

American (AMR) AF: 0.136 AC: 2081 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.0983 AC: 341 AN: 3470

East Asian (EAS) AF: 0.187 AC: 966 AN: 5178

South Asian (SAS) AF: 0.0305 AC: 147 AN: 4826

European-Finnish (FIN) AF: 0.109 AC: 1160 AN: 10604

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

European-Non Finnish (NFE) AF: 0.139 AC: 9451 AN: 68000

Other (OTH) AF: 0.165 AC: 348 AN: 2114

Alfa AF: 0.147 Hom.: 3283

Bravo AF: 0.194

Asia WGS AF: 0.105 AC: 366 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	5.4
DANN	Benign	0.93
PhyloP100		0.049
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: rs6966472; hg19: chr7-84699387;