7-85068154-C-T

Variant names:

• chr7-85068154-C-T
• rs17159594
• NM_001384900.1:c.589+37G>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.589+37G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00771 in 1,198,262 control chromosomes in the GnomAD database, including 516 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 0.035 (320 hom., cov: 32)
  • Exomes 𝑓: 0.0037 (196 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.306
• 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.118 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	NM_001384900.1	MANE Select	c.589+37G>A		intron	N/A	NP_001371829.1
	SEMA3D	NM_001384901.1		c.589+37G>A		intron	N/A	NP_001371830.1
	SEMA3D	NM_001384902.1		c.589+37G>A		intron	N/A	NP_001371831.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3D	ENST00000284136.11	TSL:5 MANE Select	c.589+37G>A		intron	N/A	ENSP00000284136.6
	SEMA3D	ENST00000444867.1	TSL:1	c.589+37G>A		intron	N/A	ENSP00000401366.1

Frequencies

GnomAD3 genomes AF: 0.0352 AC: 5354 AN: 151992 Hom.: 320 Cov.: 32

Gnomad AFR AF: 0.121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000456

Gnomad OTH AF: 0.0273

GnomAD2 exomes AF: 0.00947 AC: 2250 AN: 237708 AF XY: 0.00690

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.00575

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000257

Gnomad OTH exome AF: 0.00489

GnomAD4 exome AF: 0.00370 AC: 3875 AN: 1046152 Hom.: 196 Cov.: 13 AF XY: 0.00310 AC XY: 1670 AN XY: 538214

African (AFR) AF: 0.125 AC: 3102 AN: 24726

American (AMR) AF: 0.00643 AC: 265 AN: 41244

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22920

East Asian (EAS) AF: 0.00 AC: 0 AN: 37578

South Asian (SAS) AF: 0.000199 AC: 15 AN: 75286

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52690

Middle Eastern (MID) AF: 0.00633 AC: 31 AN: 4894

European-Non Finnish (NFE) AF: 0.000122 AC: 90 AN: 740280

Other (OTH) AF: 0.00799 AC: 372 AN: 46534

GnomAD4 genome AF: 0.0353 AC: 5367 AN: 152110 Hom.: 320 Cov.: 32 AF XY: 0.0336 AC XY: 2500 AN XY: 74372

African (AFR) AF: 0.121 AC: 5033 AN: 41496

American (AMR) AF: 0.0158 AC: 242 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3464

East Asian (EAS) AF: 0.00 AC: 0 AN: 5164

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000456 AC: 31 AN: 67964

Other (OTH) AF: 0.0270 AC: 57 AN: 2110

Alfa AF: 0.0196 Hom.: 70

Bravo AF: 0.0406

Asia WGS AF: 0.00578 AC: 20 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.1
DANN	Benign	0.73
PhyloP100		-0.31
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: rs17159594; hg19: chr7-84697470;