rs7702187

Variant names:

• chr5-9332169-T-A
• rs7702187
• NM_003966.3:c.224+5544A>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.224+5544A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.706 in 151,576 control chromosomes in the GnomAD database, including 40,229 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 (40229 hom., cov: 31)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.216
• Publications: 20 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]

SEMA5A Gene-Disease associations (from GenCC):

• neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: PanelApp Australia

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.834 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.224+5544A>T		intron	N/A	NP_003957.2	X5DR95

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.224+5544A>T		intron	N/A	ENSP00000371936.5	Q13591
	SEMA5A	ENST00000652226.1		c.224+5544A>T		intron	N/A	ENSP00000499013.1	Q13591
	SEMA5A	ENST00000897596.1		c.224+5544A>T		intron	N/A	ENSP00000567655.1

Frequencies

GnomAD3 genomes AF: 0.706 AC: 106961 AN: 151460 Hom.: 40232 Cov.: 31

Gnomad AFR AF: 0.418

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.721

Gnomad ASJ AF: 0.851

Gnomad EAS AF: 0.735

Gnomad SAS AF: 0.801

Gnomad FIN AF: 0.824

Gnomad MID AF: 0.732

Gnomad NFE AF: 0.840

Gnomad OTH AF: 0.741

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

GnomAD4 genome AF: 0.706 AC: 106986 AN: 151576 Hom.: 40229 Cov.: 31 AF XY: 0.706 AC XY: 52296 AN XY: 74084

African (AFR) AF: 0.418 AC: 17207 AN: 41176

American (AMR) AF: 0.721 AC: 11001 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.851 AC: 2953 AN: 3468

East Asian (EAS) AF: 0.735 AC: 3762 AN: 5120

South Asian (SAS) AF: 0.800 AC: 3839 AN: 4796

European-Finnish (FIN) AF: 0.824 AC: 8676 AN: 10528

Middle Eastern (MID) AF: 0.719 AC: 210 AN: 292

European-Non Finnish (NFE) AF: 0.840 AC: 57051 AN: 67932

Other (OTH) AF: 0.745 AC: 1565 AN: 2102

Alfa AF: 0.815 Hom.: 28296

Bravo AF: 0.682

Asia WGS AF: 0.713 AC: 2481 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.2
DANN	Benign	0.58
PhyloP100		0.22
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: rs7702187; hg19: chr5-9332281;