7-84002098-A-T

Variant names:

• chr7-84002098-A-T
• rs10250165
• NM_006080.3:c.1361-52T>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_006080.3(SEMA3A):​c.1361-52T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 984,588 control chromosomes in the GnomAD database, including 30,899 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.24 (4423 hom., cov: 33)
  • Exomes 𝑓: 0.25 (26476 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.328
• Publications: 5 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 7-84002098-A-T is Benign according to our data. Variant chr7-84002098-A-T is described in ClinVar as Benign. ClinVar VariationId is 1231850.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.1361-52T>A		intron_variant	Intron 11 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.1361-52T>A		intron_variant	Intron 14 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.1361-52T>A		intron_variant	Intron 15 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.1361-52T>A		intron_variant	Intron 11 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.1361-52T>A		intron_variant	Intron 12 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36115 AN: 151976 Hom.: 4424 Cov.: 33

Gnomad AFR AF: 0.249

Gnomad AMI AF: 0.247

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.250

Gnomad EAS AF: 0.161

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.300

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.228

Gnomad OTH AF: 0.231

GnomAD2 exomes AF: 0.241 AC: 51086 AN: 212320 AF XY: 0.248

Gnomad AFR exome AF: 0.248

Gnomad AMR exome AF: 0.178

Gnomad ASJ exome AF: 0.245

Gnomad EAS exome AF: 0.154

Gnomad FIN exome AF: 0.307

Gnomad NFE exome AF: 0.235

Gnomad OTH exome AF: 0.245

GnomAD4 exome AF: 0.251 AC: 209220 AN: 832492 Hom.: 26476 Cov.: 11 AF XY: 0.254 AC XY: 111104 AN XY: 437968

African (AFR) AF: 0.261 AC: 5260 AN: 20148

American (AMR) AF: 0.185 AC: 6445 AN: 34916

Ashkenazi Jewish (ASJ) AF: 0.252 AC: 5134 AN: 20370

East Asian (EAS) AF: 0.172 AC: 6106 AN: 35498

South Asian (SAS) AF: 0.329 AC: 22228 AN: 67548

European-Finnish (FIN) AF: 0.304 AC: 15578 AN: 51302

Middle Eastern (MID) AF: 0.335 AC: 1490 AN: 4446

European-Non Finnish (NFE) AF: 0.245 AC: 137247 AN: 559274

Other (OTH) AF: 0.250 AC: 9732 AN: 38990

GnomAD4 genome AF: 0.238 AC: 36126 AN: 152096 Hom.: 4423 Cov.: 33 AF XY: 0.241 AC XY: 17921 AN XY: 74340

African (AFR) AF: 0.249 AC: 10340 AN: 41500

American (AMR) AF: 0.203 AC: 3103 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.250 AC: 869 AN: 3472

East Asian (EAS) AF: 0.162 AC: 833 AN: 5154

South Asian (SAS) AF: 0.314 AC: 1512 AN: 4814

European-Finnish (FIN) AF: 0.300 AC: 3168 AN: 10572

Middle Eastern (MID) AF: 0.296 AC: 87 AN: 294

European-Non Finnish (NFE) AF: 0.228 AC: 15504 AN: 67986

Other (OTH) AF: 0.230 AC: 486 AN: 2112

Alfa AF: 0.178 Hom.: 544

Bravo AF: 0.229

Asia WGS AF: 0.234 AC: 816 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.4
DANN	Benign	0.69
PhyloP100		-0.33
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: rs10250165; hg19: chr7-83631414; COSMIC: COSV54864790;