rs433755

Positions:

• chr5-9474834-A-C

Variant summary

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

The NM_003966.3(SEMA5A):​c.-174-36982T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.52 in 152,070 control chromosomes in the GnomAD database, including 21,096 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 (21096 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.149

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=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-174-36982T>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.-174-36982T>G		intron_variant		1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-392-36982T>G		intron_variant				ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.520 AC: 79038 AN: 151948 Hom.: 21078 Cov.: 33

Gnomad AFR AF: 0.530

Gnomad AMI AF: 0.569

Gnomad AMR AF: 0.522

Gnomad ASJ AF: 0.477

Gnomad EAS AF: 0.142

Gnomad SAS AF: 0.436

Gnomad FIN AF: 0.536

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.511

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

GnomAD4 genome AF: 0.520 AC: 79091 AN: 152070 Hom.: 21096 Cov.: 33 AF XY: 0.517 AC XY: 38424 AN XY: 74346

Gnomad4 AFR AF: 0.530

Gnomad4 AMR AF: 0.521

Gnomad4 ASJ AF: 0.477

Gnomad4 EAS AF: 0.142

Gnomad4 SAS AF: 0.437

Gnomad4 FIN AF: 0.536

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.512

Alfa AF: 0.536 Hom.: 29324

Bravo AF: 0.516

Asia WGS AF: 0.341 AC: 1190 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.9
DANN	Benign	0.61

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: rs433755; hg19: chr5-9474946;