rs1806004

Positions:

• chr5-9239315-G-C

Variant summary

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

The NM_003966.3(SEMA5A):​c.271-1425C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0535 in 152,166 control chromosomes in the GnomAD database, including 293 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 0.053 (293 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0990

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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.071 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.271-1425C>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.271-1425C>G		intron_variant		1	NM_003966.3	ENSP00000371936	P1

Frequencies

GnomAD3 genomes AF: 0.0535 AC: 8140 AN: 152048 Hom.: 293 Cov.: 32

Gnomad AFR AF: 0.0150

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0519

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0774

Gnomad FIN AF: 0.0890

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.0702

Gnomad OTH AF: 0.0589

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

GnomAD4 genome AF: 0.0535 AC: 8135 AN: 152166 Hom.: 293 Cov.: 32 AF XY: 0.0535 AC XY: 3980 AN XY: 74400

Gnomad4 AFR AF: 0.0150

Gnomad4 AMR AF: 0.0517

Gnomad4 ASJ AF: 0.0844

Gnomad4 EAS AF: 0.000386

Gnomad4 SAS AF: 0.0775

Gnomad4 FIN AF: 0.0890

Gnomad4 NFE AF: 0.0702

Gnomad4 OTH AF: 0.0578

Alfa AF: 0.0609 Hom.: 38

Bravo AF: 0.0479

Asia WGS AF: 0.0250 AC: 87 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	1.6
DANN	Benign	0.64

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: rs1806004; hg19: chr5-9239427;