rs257095

Positions:

• chr5-9053833-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.2689+254G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 353,920 control chromosomes in the GnomAD database, including 134,385 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 0.88 (58489 hom., cov: 30)
  • Exomes 𝑓: 0.87 (75896 hom.)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.627

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]

MIR4636 (HGNC:41798): (microRNA 4636) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.2689+254G>A		intron_variant		ENST00000382496.10	NP_003957.2
MIR4636	NR_039779.1	n.63G>A		non_coding_transcript_exon_variant	1/1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.2689+254G>A		intron_variant		1	NM_003966.3	ENSP00000371936	P1
MIR4636	ENST00000582271.1	n.63G>A		non_coding_transcript_exon_variant	1/1
SEMA5A	ENST00000652226.1	c.2689+254G>A		intron_variant				ENSP00000499013	P1

Frequencies

GnomAD3 genomes AF: 0.877 AC: 133081 AN: 151818 Hom.: 58433 Cov.: 30

Gnomad AFR AF: 0.889

Gnomad AMI AF: 0.813

Gnomad AMR AF: 0.908

Gnomad ASJ AF: 0.817

Gnomad EAS AF: 0.963

Gnomad SAS AF: 0.871

Gnomad FIN AF: 0.863

Gnomad MID AF: 0.820

Gnomad NFE AF: 0.863

Gnomad OTH AF: 0.859

GnomAD3 exomes AF: 0.879 AC: 1078 AN: 1226 Hom.: 468 AF XY: 0.890 AC XY: 502 AN XY: 564

Gnomad AFR exome AF: 0.877

Gnomad AMR exome AF: 0.900

Gnomad ASJ exome AF: 0.864

Gnomad EAS exome AF: 0.939

Gnomad SAS exome AF: 0.833

Gnomad FIN exome AF: 0.833

Gnomad NFE exome AF: 0.874

Gnomad OTH exome AF: 0.950

GnomAD4 exome AF: 0.866 AC: 174898 AN: 201984 Hom.: 75896 Cov.: 3 AF XY: 0.865 AC XY: 88203 AN XY: 101948

Gnomad4 AFR exome AF: 0.886

Gnomad4 AMR exome AF: 0.911

Gnomad4 ASJ exome AF: 0.820

Gnomad4 EAS exome AF: 0.959

Gnomad4 SAS exome AF: 0.858

Gnomad4 FIN exome AF: 0.857

Gnomad4 NFE exome AF: 0.857

Gnomad4 OTH exome AF: 0.856

GnomAD4 genome AF: 0.877 AC: 133198 AN: 151936 Hom.: 58489 Cov.: 30 AF XY: 0.877 AC XY: 65153 AN XY: 74264

Gnomad4 AFR AF: 0.889

Gnomad4 AMR AF: 0.908

Gnomad4 ASJ AF: 0.817

Gnomad4 EAS AF: 0.963

Gnomad4 SAS AF: 0.871

Gnomad4 FIN AF: 0.863

Gnomad4 NFE AF: 0.863

Gnomad4 OTH AF: 0.859

Alfa AF: 0.863 Hom.: 73710

Bravo AF: 0.880

Asia WGS AF: 0.907 AC: 3154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	1.6
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: rs257095; hg19: chr5-9053945;