rs8036030

Variant names:

• chr15-74424268-A-G
• rs8036030
• NM_003612.5:c.179-5316T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 15 publications found

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]

SEMA7A Gene-Disease associations (from GenCC):

• cholestasis, progressive familial intrahepatic, 11

  Inheritance: AR 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=-0.92).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.598 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003612.5. 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
	SEMA7A	NM_003612.5	MANE Select	c.179-5316T>C		intron	N/A	NP_003603.1	O75326-1
	SEMA7A	NM_001146029.3		c.179-5316T>C		intron	N/A	NP_001139501.1	O75326-2
	SEMA7A	NM_001146030.3		c.-317-5316T>C		intron	N/A	NP_001139502.1	F5GYX3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SEMA7A	ENST00000261918.9	TSL:1 MANE Select	c.179-5316T>C		intron	N/A	ENSP00000261918.4	O75326-1
	SEMA7A	ENST00000543145.6	TSL:2	c.179-5316T>C		intron	N/A	ENSP00000438966.2	O75326-2
	SEMA7A	ENST00000542748.6	TSL:5	c.-317-5316T>C		intron	N/A	ENSP00000441493.1	F5GYX3

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

African (AFR) AF: 0.200 AC: 8303 AN: 41440

American (AMR) AF: 0.591 AC: 9014 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.539 AC: 1869 AN: 3466

East Asian (EAS) AF: 0.566 AC: 2922 AN: 5162

South Asian (SAS) AF: 0.470 AC: 2263 AN: 4812

European-Finnish (FIN) AF: 0.569 AC: 6001 AN: 10542

Middle Eastern (MID) AF: 0.588 AC: 173 AN: 294

European-Non Finnish (NFE) AF: 0.603 AC: 40971 AN: 67952

Other (OTH) AF: 0.503 AC: 1060 AN: 2106

Alfa AF: 0.498 Hom.: 19595

Bravo AF: 0.474

Asia WGS AF: 0.548 AC: 1906 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	1.7
DANN	Benign	0.28
PhyloP100		-1.9
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: rs8036030; hg19: chr15-74716609;