7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATAT

Position:

• chr7-85055645-CATATATATATATATATATATATATATATAT-CATATATATATATATATATATATATATATATATATAT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001384900.1(SEMA3D):​c.861+66_861+71dupATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0121 in 159,480 control chromosomes in the GnomAD database, including 32 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.017 (32 hom., cov: 0)
  • Exomes 𝑓: 0.00089 (0 hom.)
• Consequence: SEMA3D NM_001384900.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.0169 (1882/111350) while in subpopulation EAS AF= 0.0285 (102/3582). AF 95% confidence interval is 0.024. There are 32 homozygotes in gnomad4. There are 891 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 32 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3D	NM_001384900.1	c.861+66_861+71dupATATAT		intron_variant		ENST00000284136.11	NP_001371829.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3D	ENST00000284136.11	c.861+66_861+71dupATATAT		intron_variant		5	NM_001384900.1	ENSP00000284136.6
SEMA3D	ENST00000444867.1	c.861+66_861+71dupATATAT		intron_variant		1		ENSP00000401366.1
SEMA3D	ENST00000463315.1	n.49+66_49+71dupATATAT		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0169 AC: 1881 AN: 111348 Hom.: 32 Cov.: 0

Gnomad AFR AF: 0.0102

Gnomad AMI AF: 0.00900

Gnomad AMR AF: 0.0235

Gnomad ASJ AF: 0.0190

Gnomad EAS AF: 0.0286

Gnomad SAS AF: 0.0281

Gnomad FIN AF: 0.00742

Gnomad MID AF: 0.0196

Gnomad NFE AF: 0.0185

Gnomad OTH AF: 0.0199

GnomAD4 exome AF: 0.000893 AC: 43 AN: 48130 Hom.: 0 AF XY: 0.00104 AC XY: 29 AN XY: 27790

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00517

Gnomad4 ASJ exome AF: 0.00140

Gnomad4 EAS exome AF: 0.00193

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000836

Gnomad4 OTH exome AF: 0.00108

GnomAD4 genome AF: 0.0169 AC: 1882 AN: 111350 Hom.: 32 Cov.: 0 AF XY: 0.0172 AC XY: 891 AN XY: 51678

Gnomad4 AFR AF: 0.0102

Gnomad4 AMR AF: 0.0237

Gnomad4 ASJ AF: 0.0190

Gnomad4 EAS AF: 0.0285

Gnomad4 SAS AF: 0.0282

Gnomad4 FIN AF: 0.00742

Gnomad4 NFE AF: 0.0185

Gnomad4 OTH AF: 0.0205

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs56131427; hg19: chr7-84684961;