7-84002133-CAAAG-C

Position:

• chr7-84002133-CAAAG-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000265362.9(SEMA3A):​c.1361-91_1361-88del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.237 in 717,676 control chromosomes in the GnomAD database, including 21,059 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4271 hom., cov: 24)
  • Exomes 𝑓: 0.24 (16788 hom.)
• Consequence: SEMA3A ENST00000265362.9 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.04

Genes affected

SEMA3A (HGNC:10723): (semaphorin 3A) This gene is a member of the semaphorin family and encodes a protein with an Ig-like C2-type (immunoglobulin-like) domain, a PSI domain and a Sema domain. This secreted protein can function as either a chemorepulsive agent, inhibiting axonal outgrowth, or as a chemoattractive agent, stimulating the growth of apical dendrites. In both cases, the protein is vital for normal neuronal pattern development. Increased expression of this protein is associated with schizophrenia and is seen in a variety of human tumor cell lines. Also, aberrant release of this protein is associated with the progression of Alzheimer's disease. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 7-84002133-CAAAG-C is Benign according to our data. Variant chr7-84002133-CAAAG-C is described in ClinVar as [Benign]. Clinvar id is 1248345.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.3 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1361-91_1361-88del		intron_variant		ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1361-91_1361-88del		intron_variant			XP_005250167.1
SEMA3A	XM_047419751.1	c.1361-91_1361-88del		intron_variant			XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-91_1361-88del		intron_variant		1	NM_006080.3	ENSP00000265362	P1
SEMA3A	ENST00000436949.5	c.1361-91_1361-88del		intron_variant		5		ENSP00000415260	P1

Frequencies

GnomAD3 genomes AF: 0.234 AC: 35577 AN: 151796 Hom.: 4272 Cov.: 24

Gnomad AFR AF: 0.239

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.299

Gnomad MID AF: 0.309

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.228

GnomAD4 exome AF: 0.238 AC: 134744 AN: 565762 Hom.: 16788 AF XY: 0.242 AC XY: 72362 AN XY: 299540

Gnomad4 AFR exome AF: 0.238

Gnomad4 AMR exome AF: 0.178

Gnomad4 ASJ exome AF: 0.246

Gnomad4 EAS exome AF: 0.171

Gnomad4 SAS exome AF: 0.323

Gnomad4 FIN exome AF: 0.300

Gnomad4 NFE exome AF: 0.228

Gnomad4 OTH exome AF: 0.236

GnomAD4 genome AF: 0.234 AC: 35586 AN: 151914 Hom.: 4271 Cov.: 24 AF XY: 0.238 AC XY: 17668 AN XY: 74246

Gnomad4 AFR AF: 0.239

Gnomad4 AMR AF: 0.202

Gnomad4 ASJ AF: 0.250

Gnomad4 EAS AF: 0.161

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.299

Gnomad4 NFE AF: 0.228

Gnomad4 OTH AF: 0.227

Alfa AF: 0.237 Hom.: 542

Bravo AF: 0.226

Asia WGS AF: 0.233 AC: 812 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 09, 2018

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs3832523; hg19: chr7-83631449;