rs8036030

Positions:

• chr15-74424268-A-G
• chr15-74424268-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003612.5(SEMA7A):​c.179-5316T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.48 in 151,948 control chromosomes in the GnomAD database, including 19,913 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 0.48 (19913 hom., cov: 31)
• Consequence: SEMA7A NM_003612.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.87

Genes affected

SEMA7A (HGNC:10741): (semaphorin 7A (JohnMiltonHagen blood group)) This gene encodes a member of the semaphorin family of proteins. The encoded preproprotein is proteolytically processed to generate the mature glycosylphosphatidylinositol (GPI)-anchored membrane glycoprotein. The encoded protein is found on activated lymphocytes and erythrocytes and may be involved in immunomodulatory and neuronal processes. The encoded protein carries the John Milton Hagen (JMH) blood group antigens. Mutations in this gene may be associated with reduced bone mineral density (BMD). Alternative splicing results in multiple transcript variants, at least one of which encodes an isoform that is proteolytically processed. [provided by RefSeq, Feb 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SEMA7A	NM_003612.5	c.179-5316T>C		intron_variant		ENST00000261918.9
SEMA7A	NM_001146029.3	c.179-5316T>C		intron_variant
SEMA7A	NM_001146030.3	c.-317-5316T>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SEMA7A	ENST00000261918.9	c.179-5316T>C		intron_variant		1	NM_003612.5	P1
SEMA7A	ENST00000542748.6	c.-317-5316T>C		intron_variant		5
SEMA7A	ENST00000543145.6	c.179-5316T>C		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.480 AC: 72911 AN: 151830 Hom.: 19892 Cov.: 31

Gnomad AFR AF: 0.200

Gnomad AMI AF: 0.425

Gnomad AMR AF: 0.590

Gnomad ASJ AF: 0.539

Gnomad EAS AF: 0.566

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.569

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.603

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.480 AC: 72964 AN: 151948 Hom.: 19913 Cov.: 31 AF XY: 0.480 AC XY: 35620 AN XY: 74258

Gnomad4 AFR AF: 0.200

Gnomad4 AMR AF: 0.591

Gnomad4 ASJ AF: 0.539

Gnomad4 EAS AF: 0.566

Gnomad4 SAS AF: 0.470

Gnomad4 FIN AF: 0.569

Gnomad4 NFE AF: 0.603

Gnomad4 OTH AF: 0.503

Alfa AF: 0.530 Hom.: 10705

Bravo AF: 0.474

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.28

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

Publications

LitVar

Other links and lift over

dbSNP: rs8036030; hg19: chr15-74716609;