chr7-83985304-T-G

Variant names:

• chr7-83985304-T-G
• rs17246251
• NM_006080.3:c.1494+132A>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_006080.3(SEMA3A):​c.1494+132A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.381 in 630,146 control chromosomes in the GnomAD database, including 49,472 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.38 (11626 hom., cov: 32)
  • Exomes 𝑓: 0.38 (37846 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.115
• Publications: 1 publications found

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]

SEMA3A Gene-Disease associations (from GenCC):

• skeletal dysplasia

  Inheritance: AR Classification: DEFINITIVE Submitted by: G2P
• hypogonadotropic hypogonadism 16 with or without anosmia

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
• multiple congenital anomalies/dysmorphic syndrome

  Inheritance: AR Classification: MODERATE Submitted by: Ambry Genetics
• Brugada syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Kallmann syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-83985304-T-G is Benign according to our data. Variant chr7-83985304-T-G is described in ClinVar as Benign. ClinVar VariationId is 1245431.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.434 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006080.3. 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
	SEMA3A	NM_006080.3	MANE Select	c.1494+132A>C		intron	N/A	NP_006071.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA3A	ENST00000265362.9	TSL:1 MANE Select	c.1494+132A>C		intron	N/A	ENSP00000265362.3
	SEMA3A	ENST00000436949.5	TSL:5	c.1494+132A>C		intron	N/A	ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.382 AC: 58023 AN: 151856 Hom.: 11629 Cov.: 32

Gnomad AFR AF: 0.354

Gnomad AMI AF: 0.553

Gnomad AMR AF: 0.322

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.0589

Gnomad SAS AF: 0.240

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.478

Gnomad NFE AF: 0.438

Gnomad OTH AF: 0.408

GnomAD4 exome AF: 0.381 AC: 182223 AN: 478174 Hom.: 37846 AF XY: 0.378 AC XY: 96213 AN XY: 254776

African (AFR) AF: 0.356 AC: 4076 AN: 11464

American (AMR) AF: 0.239 AC: 4321 AN: 18064

Ashkenazi Jewish (ASJ) AF: 0.370 AC: 4967 AN: 13436

East Asian (EAS) AF: 0.0526 AC: 1542 AN: 29326

South Asian (SAS) AF: 0.247 AC: 10119 AN: 40972

European-Finnish (FIN) AF: 0.419 AC: 15508 AN: 37040

Middle Eastern (MID) AF: 0.435 AC: 850 AN: 1952

European-Non Finnish (NFE) AF: 0.436 AC: 130903 AN: 300086

Other (OTH) AF: 0.385 AC: 9937 AN: 25834

GnomAD4 genome AF: 0.382 AC: 58041 AN: 151972 Hom.: 11626 Cov.: 32 AF XY: 0.375 AC XY: 27855 AN XY: 74296

African (AFR) AF: 0.354 AC: 14658 AN: 41454

American (AMR) AF: 0.322 AC: 4908 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.375 AC: 1301 AN: 3468

East Asian (EAS) AF: 0.0590 AC: 306 AN: 5186

South Asian (SAS) AF: 0.240 AC: 1156 AN: 4818

European-Finnish (FIN) AF: 0.421 AC: 4437 AN: 10548

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.438 AC: 29771 AN: 67924

Other (OTH) AF: 0.406 AC: 856 AN: 2108

Alfa AF: 0.265 Hom.: 680

Bravo AF: 0.374

Asia WGS AF: 0.172 AC: 599 AN: 3474

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	1.8
DANN	Benign	0.64
PhyloP100		0.12
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: rs17246251; hg19: chr7-83614620;