rs268521

Positions:

• chr5-9487836-T-C
• chr5-9487836-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003966.3(SEMA5A):​c.-174-49984A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.968 in 152,202 control chromosomes in the GnomAD database, including 71,605 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.97 (71605 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.40

Genes affected

SEMA5A (HGNC:10736): (semaphorin 5A) This gene belongs to the semaphorin gene family that encodes membrane proteins containing a semaphorin domain and several thrombospondin type-1 repeats. Members of this family are involved in axonal guidance during neural development. This gene has been implicated as an autism susceptibility gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.02).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.988 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-174-49984A>G		intron_variant		ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-174-49984A>G		intron_variant		1	NM_003966.3	ENSP00000371936	P1
SEMA5A	ENST00000652226.1	c.-392-49984A>G		intron_variant				ENSP00000499013	P1

Frequencies

GnomAD3 genomes AF: 0.968 AC: 147274 AN: 152084 Hom.: 71551 Cov.: 32

Gnomad AFR AF: 0.967

Gnomad AMI AF: 0.970

Gnomad AMR AF: 0.952

Gnomad ASJ AF: 0.986

Gnomad EAS AF: 0.704

Gnomad SAS AF: 0.877

Gnomad FIN AF: 0.995

Gnomad MID AF: 0.959

Gnomad NFE AF: 0.994

Gnomad OTH AF: 0.971

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.968 AC: 147385 AN: 152202 Hom.: 71605 Cov.: 32 AF XY: 0.964 AC XY: 71736 AN XY: 74394

Gnomad4 AFR AF: 0.967

Gnomad4 AMR AF: 0.952

Gnomad4 ASJ AF: 0.986

Gnomad4 EAS AF: 0.704

Gnomad4 SAS AF: 0.877

Gnomad4 FIN AF: 0.995

Gnomad4 NFE AF: 0.994

Gnomad4 OTH AF: 0.971

Alfa AF: 0.979 Hom.: 6381

Bravo AF: 0.965

Asia WGS AF: 0.845 AC: 2938 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.56
DANN	Benign	0.48

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: rs268521; hg19: chr5-9487948;