chr5-9416944-G-C

Variant names:

• chr5-9416944-G-C
• rs368226
• NM_003966.3:c.-78+20812C>G

Variant summary

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

The NM_003966.3(SEMA5A):​c.-78+20812C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.893 in 152,266 control chromosomes in the GnomAD database, including 61,230 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 (61230 hom., cov: 33)
• Consequence: SEMA5A NM_003966.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.533
• 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]

ENSG00000248537 (HGNC:40519):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.01).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.928 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	NM_003966.3	MANE Select	c.-78+20812C>G		intron	N/A	NP_003957.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA5A	ENST00000382496.10	TSL:1 MANE Select	c.-78+20812C>G		intron	N/A	ENSP00000371936.5
	SEMA5A	ENST00000652226.1		c.-78+4733C>G		intron	N/A	ENSP00000499013.1
	ENSG00000248537	ENST00000511310.1	TSL:2	n.258-5404G>C		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.893 AC: 135909 AN: 152148 Hom.: 61196 Cov.: 33

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.998

Gnomad AMR AF: 0.745

Gnomad ASJ AF: 0.965

Gnomad EAS AF: 0.705

Gnomad SAS AF: 0.825

Gnomad FIN AF: 0.955

Gnomad MID AF: 0.968

Gnomad NFE AF: 0.934

Gnomad OTH AF: 0.886

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

GnomAD4 genome AF: 0.893 AC: 135994 AN: 152266 Hom.: 61230 Cov.: 33 AF XY: 0.889 AC XY: 66163 AN XY: 74452

African (AFR) AF: 0.888 AC: 36880 AN: 41542

American (AMR) AF: 0.745 AC: 11392 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.965 AC: 3352 AN: 3472

East Asian (EAS) AF: 0.704 AC: 3640 AN: 5168

South Asian (SAS) AF: 0.825 AC: 3980 AN: 4822

European-Finnish (FIN) AF: 0.955 AC: 10149 AN: 10624

Middle Eastern (MID) AF: 0.966 AC: 284 AN: 294

European-Non Finnish (NFE) AF: 0.934 AC: 63546 AN: 68024

Other (OTH) AF: 0.881 AC: 1861 AN: 2112

Alfa AF: 0.918 Hom.: 3116

Bravo AF: 0.876

Asia WGS AF: 0.754 AC: 2624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	0.42
DANN	Benign	0.60
PhyloP100		-0.53
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: rs368226; hg19: chr5-9417056;