rs17559084

Variant names:

• chr7-85015184-C-T
• rs17559084
• NM_001384900.1:c.1578G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_001384900.1(SEMA3D):​c.1578G>A​(p.Leu526Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.296 in 1,609,492 control chromosomes in the GnomAD database, including 76,133 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.23 (4880 hom., cov: 32)
  • Exomes 𝑓: 0.30 (71253 hom.)
• Consequence: SEMA3D NM_001384900.1 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: 0.516
• Publications: 18 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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BP6: Variant 7-85015184-C-T is Benign according to our data. Variant chr7-85015184-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060649.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=0.516 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.327 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.1578G>A	p.Leu526Leu	synonymous	Exon 16 of 19	NP_001371829.1	O95025
	SEMA3D	NM_001384901.1		c.1578G>A	p.Leu526Leu	synonymous	Exon 17 of 20	NP_001371830.1	O95025
	SEMA3D	NM_001384902.1		c.1578G>A	p.Leu526Leu	synonymous	Exon 18 of 21	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.1578G>A	p.Leu526Leu	synonymous	Exon 16 of 19	ENSP00000284136.6	O95025
	SEMA3D	ENST00000484038.1	TSL:1	n.704G>A		non_coding_transcript_exon	Exon 7 of 10
	SEMA3D	ENST00000916323.1		c.1578G>A	p.Leu526Leu	synonymous	Exon 15 of 18	ENSP00000586382.1

Frequencies

GnomAD3 genomes AF: 0.231 AC: 34977 AN: 151626 Hom.: 4883 Cov.: 32

Gnomad AFR AF: 0.0857

Gnomad AMI AF: 0.356

Gnomad AMR AF: 0.222

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0632

Gnomad SAS AF: 0.187

Gnomad FIN AF: 0.230

Gnomad MID AF: 0.301

Gnomad NFE AF: 0.330

Gnomad OTH AF: 0.255

GnomAD2 exomes AF: 0.242 AC: 60343 AN: 249844 AF XY: 0.250

Gnomad AFR exome AF: 0.0796

Gnomad AMR exome AF: 0.148

Gnomad ASJ exome AF: 0.287

Gnomad EAS exome AF: 0.0625

Gnomad FIN exome AF: 0.235

Gnomad NFE exome AF: 0.330

Gnomad OTH exome AF: 0.275

GnomAD4 exome AF: 0.303 AC: 441624 AN: 1457750 Hom.: 71253 Cov.: 34 AF XY: 0.301 AC XY: 218397 AN XY: 725132

African (AFR) AF: 0.0764 AC: 2543 AN: 33296

American (AMR) AF: 0.156 AC: 6935 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.294 AC: 7627 AN: 25980

East Asian (EAS) AF: 0.0540 AC: 2141 AN: 39642

South Asian (SAS) AF: 0.197 AC: 16967 AN: 86042

European-Finnish (FIN) AF: 0.237 AC: 12641 AN: 53354

Middle Eastern (MID) AF: 0.292 AC: 1676 AN: 5746

European-Non Finnish (NFE) AF: 0.338 AC: 374381 AN: 1109002

Other (OTH) AF: 0.278 AC: 16713 AN: 60134

GnomAD4 genome AF: 0.230 AC: 34968 AN: 151742 Hom.: 4880 Cov.: 32 AF XY: 0.225 AC XY: 16704 AN XY: 74140

African (AFR) AF: 0.0854 AC: 3542 AN: 41460

American (AMR) AF: 0.221 AC: 3368 AN: 15220

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1067 AN: 3468

East Asian (EAS) AF: 0.0632 AC: 323 AN: 5114

South Asian (SAS) AF: 0.187 AC: 901 AN: 4816

European-Finnish (FIN) AF: 0.230 AC: 2430 AN: 10570

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.330 AC: 22389 AN: 67782

Other (OTH) AF: 0.253 AC: 533 AN: 2108

Alfa AF: 0.306 Hom.: 14009

Bravo AF: 0.221

Asia WGS AF: 0.118 AC: 413 AN: 3478

EpiCase AF: 0.335

EpiControl AF: 0.329

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA3D-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	9.0
DANN	Benign	0.87
PhyloP100		0.52
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs17559084; hg19: chr7-84644500; COSMIC: COSV52393702;