5-9161300-A-G

Variant names:

• chr5-9161300-A-G
• rs3846574
• NM_003966.3:c.1274-6605T>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.1274-6605T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.608 in 151,812 control chromosomes in the GnomAD database, including 28,346 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 0.61 (28346 hom., cov: 30)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.15
• 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=-0.99).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.641 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SEMA5A	NM_003966.3	c.1274-6605T>C		intron_variant	Intron 11 of 22	ENST00000382496.10	NP_003957.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SEMA5A	ENST00000382496.10	c.1274-6605T>C		intron_variant	Intron 11 of 22	1	NM_003966.3	ENSP00000371936.5
SEMA5A	ENST00000652226.1	c.1274-6605T>C		intron_variant	Intron 13 of 24			ENSP00000499013.1

Frequencies

GnomAD3 genomes AF: 0.608 AC: 92304 AN: 151692 Hom.: 28346 Cov.: 30

Gnomad AFR AF: 0.593

Gnomad AMI AF: 0.815

Gnomad AMR AF: 0.563

Gnomad ASJ AF: 0.707

Gnomad EAS AF: 0.442

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.590

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.646

Gnomad OTH AF: 0.623

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

GnomAD4 genome AF: 0.608 AC: 92329 AN: 151812 Hom.: 28346 Cov.: 30 AF XY: 0.602 AC XY: 44637 AN XY: 74158

African (AFR) AF: 0.592 AC: 24502 AN: 41376

American (AMR) AF: 0.562 AC: 8569 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.707 AC: 2453 AN: 3470

East Asian (EAS) AF: 0.443 AC: 2282 AN: 5148

South Asian (SAS) AF: 0.459 AC: 2202 AN: 4802

European-Finnish (FIN) AF: 0.590 AC: 6207 AN: 10512

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.646 AC: 43893 AN: 67938

Other (OTH) AF: 0.617 AC: 1305 AN: 2114

Alfa AF: 0.628 Hom.: 54575

Bravo AF: 0.606

Asia WGS AF: 0.415 AC: 1441 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.12
DANN	Benign	0.24
PhyloP100		-3.2
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: rs3846574; hg19: chr5-9161412;