rs571826

Positions:

• chr5-9460341-G-A

Variant summary

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

The NM_003966.3(SEMA5A):​c.-174-22489C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 151,116 control chromosomes in the GnomAD database, including 2,547 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 0.15 (2547 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.109

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.314 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-174-22489C>T		intron_variant		ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-174-22489C>T		intron_variant		1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-392-22489C>T		intron_variant				ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.150 AC: 22592 AN: 151002 Hom.: 2530 Cov.: 33

Gnomad AFR AF: 0.318

Gnomad AMI AF: 0.0292

Gnomad AMR AF: 0.104

Gnomad ASJ AF: 0.0789

Gnomad EAS AF: 0.0425

Gnomad SAS AF: 0.105

Gnomad FIN AF: 0.0926

Gnomad MID AF: 0.0617

Gnomad NFE AF: 0.0835

Gnomad OTH AF: 0.125

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

GnomAD4 genome AF: 0.150 AC: 22666 AN: 151116 Hom.: 2547 Cov.: 33 AF XY: 0.148 AC XY: 10922 AN XY: 73790

Gnomad4 AFR AF: 0.318

Gnomad4 AMR AF: 0.104

Gnomad4 ASJ AF: 0.0789

Gnomad4 EAS AF: 0.0424

Gnomad4 SAS AF: 0.105

Gnomad4 FIN AF: 0.0926

Gnomad4 NFE AF: 0.0835

Gnomad4 OTH AF: 0.132

Alfa AF: 0.132 Hom.: 197

Bravo AF: 0.154

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.3
DANN	Benign	0.35

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: rs571826; hg19: chr5-9460453;