rs2272221

Variant names:

• chr7-84014371-G-A
• rs2272221
• NM_006080.3:c.668-20C>T

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.668-20C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 1,560,980 control chromosomes in the GnomAD database, including 95,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (16120 hom., cov: 32)
  • Exomes 𝑓: 0.33 (79324 hom.)
• Consequence: SEMA3A NM_006080.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 0.188

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 7-84014371-G-A is Benign according to our data. Variant chr7-84014371-G-A is described in ClinVar as [Benign]. Clinvar id is 1174858.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr7-84014371-G-A is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA3A	NM_006080.3	c.668-20C>T		intron_variant	Intron 6 of 16	ENST00000265362.9	NP_006071.1
SEMA3A	XM_005250110.4	c.668-20C>T		intron_variant	Intron 9 of 19		XP_005250167.1
SEMA3A	XM_047419751.1	c.668-20C>T		intron_variant	Intron 10 of 20		XP_047275707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA3A	ENST00000265362.9	c.668-20C>T		intron_variant	Intron 6 of 16	1	NM_006080.3	ENSP00000265362.3
SEMA3A	ENST00000436949.5	c.668-20C>T		intron_variant	Intron 7 of 17	5		ENSP00000415260.1

Frequencies

GnomAD3 genomes AF: 0.431 AC: 65317 AN: 151406 Hom.: 16094 Cov.: 32

Gnomad AFR AF: 0.692

Gnomad AMI AF: 0.289

Gnomad AMR AF: 0.362

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.363

Gnomad SAS AF: 0.454

Gnomad FIN AF: 0.343

Gnomad MID AF: 0.383

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.395

GnomAD2 exomes AF: 0.366 AC: 89518 AN: 244800 AF XY: 0.364

Gnomad AFR exome AF: 0.695

Gnomad AMR exome AF: 0.336

Gnomad ASJ exome AF: 0.330

Gnomad EAS exome AF: 0.343

Gnomad FIN exome AF: 0.352

Gnomad NFE exome AF: 0.312

Gnomad OTH exome AF: 0.346

GnomAD4 exome AF: 0.326 AC: 459567 AN: 1409458 Hom.: 79324 Cov.: 26 AF XY: 0.329 AC XY: 231716 AN XY: 703954

Gnomad4 AFR exome AF: 0.697 AC: 21933 AN: 31462

Gnomad4 AMR exome AF: 0.340 AC: 14991 AN: 44108

Gnomad4 ASJ exome AF: 0.332 AC: 8541 AN: 25744

Gnomad4 EAS exome AF: 0.390 AC: 15312 AN: 39280

Gnomad4 SAS exome AF: 0.457 AC: 38613 AN: 84484

Gnomad4 FIN exome AF: 0.354 AC: 17785 AN: 50196

Gnomad4 NFE exome AF: 0.299 AC: 319766 AN: 1069908

Gnomad4 Remaining exome AF: 0.348 AC: 20386 AN: 58616

GnomAD4 genome AF: 0.432 AC: 65395 AN: 151522 Hom.: 16120 Cov.: 32 AF XY: 0.433 AC XY: 32023 AN XY: 74022

Gnomad4 AFR AF: 0.692 AC: 0.69183 AN: 0.69183

Gnomad4 AMR AF: 0.362 AC: 0.362085 AN: 0.362085

Gnomad4 ASJ AF: 0.346 AC: 0.345643 AN: 0.345643

Gnomad4 EAS AF: 0.364 AC: 0.363566 AN: 0.363566

Gnomad4 SAS AF: 0.454 AC: 0.454413 AN: 0.454413

Gnomad4 FIN AF: 0.343 AC: 0.343398 AN: 0.343398

Gnomad4 NFE AF: 0.314 AC: 0.313984 AN: 0.313984

Gnomad4 OTH AF: 0.395 AC: 0.394787 AN: 0.394787

Alfa AF: 0.370 Hom.: 2134

Bravo AF: 0.443

Asia WGS AF: 0.440 AC: 1531 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Aug 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified Benign:2

-

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.8
DANN	Benign	0.63
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

Publications

LitVar

Other links and lift over

dbSNP: rs2272221; hg19: chr7-83643687;