rs16882871

chr5-9479510-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.-174-41658G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0777 in 152,186 control chromosomes in the GnomAD database, including 493 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 0.078 (493 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0480

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=-0.88).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0877 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA5A	NM_003966.3	c.-174-41658G>A		intron_variant		ENST00000382496.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-174-41658G>A		intron_variant		1	NM_003966.3	P1
SEMA5A	ENST00000652226.1	c.-392-41658G>A		intron_variant				P1

Frequencies

GnomAD3 genomes AF: 0.0776 AC: 11799 AN: 152068 Hom.: 486 Cov.: 32

Gnomad AFR AF: 0.0733

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0727

Gnomad ASJ AF: 0.0746

Gnomad EAS AF: 0.0419

Gnomad SAS AF: 0.0951

Gnomad FIN AF: 0.0925

Gnomad MID AF: 0.0348

Gnomad NFE AF: 0.0817

Gnomad OTH AF: 0.0703

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

GnomAD4 genome AF: 0.0777 AC: 11832 AN: 152186 Hom.: 493 Cov.: 32 AF XY: 0.0778 AC XY: 5789 AN XY: 74400

Gnomad4 AFR AF: 0.0737

Gnomad4 AMR AF: 0.0725

Gnomad4 ASJ AF: 0.0746

Gnomad4 EAS AF: 0.0418

Gnomad4 SAS AF: 0.0949

Gnomad4 FIN AF: 0.0925

Gnomad4 NFE AF: 0.0817

Gnomad4 OTH AF: 0.0781

Alfa AF: 0.0776 Hom.: 204

Bravo AF: 0.0727

Asia WGS AF: 0.129 AC: 452 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
Cadd	Benign	3.7
Dann	Benign	0.62

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: rs16882871; hg19: chr5-9479622;