rs3756726

Variant names:

• chr5-9452607-C-G
• rs3756726
• NM_003966.3:c.-174-14755G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003966.3(SEMA5A):​c.-174-14755G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.708 in 152,084 control chromosomes in the GnomAD database, including 38,696 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 0.71 (38696 hom., cov: 32)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.760
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.77 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003966.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	NM_003966.3	MANE Select	c.-174-14755G>C		intron	N/A	NP_003957.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.-174-14755G>C		intron	N/A	ENSP00000371936.5
	SEMA5A	ENST00000652226.1		c.-392-14755G>C		intron	N/A	ENSP00000499013.1
	SEMA5A	ENST00000897596.1		c.-247-14755G>C		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.708 AC: 107550 AN: 151968 Hom.: 38687 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.799

Gnomad AMR AF: 0.761

Gnomad ASJ AF: 0.763

Gnomad EAS AF: 0.695

Gnomad SAS AF: 0.726

Gnomad FIN AF: 0.756

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.775

Gnomad OTH AF: 0.697

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

GnomAD4 genome AF: 0.708 AC: 107601 AN: 152084 Hom.: 38696 Cov.: 32 AF XY: 0.709 AC XY: 52710 AN XY: 74320

African (AFR) AF: 0.558 AC: 23130 AN: 41460

American (AMR) AF: 0.761 AC: 11642 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.763 AC: 2648 AN: 3472

East Asian (EAS) AF: 0.694 AC: 3585 AN: 5164

South Asian (SAS) AF: 0.726 AC: 3490 AN: 4806

European-Finnish (FIN) AF: 0.756 AC: 7994 AN: 10574

Middle Eastern (MID) AF: 0.677 AC: 199 AN: 294

European-Non Finnish (NFE) AF: 0.775 AC: 52710 AN: 68002

Other (OTH) AF: 0.700 AC: 1474 AN: 2106

Alfa AF: 0.741 Hom.: 5273

Bravo AF: 0.703

Asia WGS AF: 0.688 AC: 2394 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.28
DANN	Benign	0.30
PhyloP100		-0.76
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3756726; hg19: chr5-9452719;