rs2256569

Positions:

• chr5-9160268-C-T

Variant summary

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

The NM_003966.3(SEMA5A):​c.1274-5573G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 151,952 control chromosomes in the GnomAD database, including 23,724 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 0.52 (23724 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00800

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.684 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3	c.1274-5573G>A		intron_variant		ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5A	ENST00000382496.10	c.1274-5573G>A		intron_variant		1	NM_003966.3	P1
SEMA5A	ENST00000652226.1	c.1274-5573G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.519 AC: 78736 AN: 151834 Hom.: 23737 Cov.: 32

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.797

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.727

Gnomad EAS AF: 0.270

Gnomad SAS AF: 0.572

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.689

Gnomad OTH AF: 0.551

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

GnomAD4 genome AF: 0.518 AC: 78714 AN: 151952 Hom.: 23724 Cov.: 32 AF XY: 0.516 AC XY: 38253 AN XY: 74202

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.470

Gnomad4 ASJ AF: 0.727

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.570

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.689

Gnomad4 OTH AF: 0.546

Alfa AF: 0.655 Hom.: 55536

Bravo AF: 0.489

Asia WGS AF: 0.386 AC: 1341 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.0
DANN	Benign	0.68

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: rs2256569; hg19: chr5-9160380;