rs446732

Variant names:

• chr5-9507660-G-A
• rs446732
• NM_003966.3:c.-175+37924C>T

Variant summary

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

The NM_003966.3(SEMA5A):​c.-175+37924C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.89 in 152,156 control chromosomes in the GnomAD database, including 60,548 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 0.89 (60548 hom., cov: 31)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.14
• 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=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.908 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.-175+37924C>T		intron_variant	Intron 1 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.-175+37924C>T		intron_variant	Intron 1 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.-393+37924C>T		intron_variant	Intron 1 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.891 AC: 135416 AN: 152038 Hom.: 60520 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.973

Gnomad AMR AF: 0.884

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.643

Gnomad SAS AF: 0.819

Gnomad FIN AF: 0.903

Gnomad MID AF: 0.940

Gnomad NFE AF: 0.914

Gnomad OTH AF: 0.900

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

GnomAD4 genome AF: 0.890 AC: 135493 AN: 152156 Hom.: 60548 Cov.: 31 AF XY: 0.887 AC XY: 65946 AN XY: 74368

African (AFR) AF: 0.885 AC: 36754 AN: 41514

American (AMR) AF: 0.884 AC: 13513 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.917 AC: 3179 AN: 3468

East Asian (EAS) AF: 0.644 AC: 3318 AN: 5152

South Asian (SAS) AF: 0.819 AC: 3936 AN: 4806

European-Finnish (FIN) AF: 0.903 AC: 9556 AN: 10586

Middle Eastern (MID) AF: 0.949 AC: 279 AN: 294

European-Non Finnish (NFE) AF: 0.914 AC: 62190 AN: 68020

Other (OTH) AF: 0.892 AC: 1883 AN: 2112

Alfa AF: 0.903 Hom.: 8029

Bravo AF: 0.891

Asia WGS AF: 0.718 AC: 2494 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.23
DANN	Benign	0.63
PhyloP100		-2.1
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: rs446732; hg19: chr5-9507772;