15-74411588-T-C

Variant names:

• chr15-74411588-T-C
• rs741761
• NM_003612.5:c.1545A>G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6 BP7 BA1

The NM_003612.5(SEMA7A):​c.1545A>G​(p.Gln515Gln) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 1,588,012 control chromosomes in the GnomAD database, including 83,786 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.39 (14129 hom., cov: 32)
  • Exomes 𝑓: 0.29 (69657 hom.)
• Consequence: SEMA7A NM_003612.5 synonymous
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -1.37
• Publications: 21 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]

MIR6881 (HGNC:50098): (microRNA 6881) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 15-74411588-T-C is Benign according to our data. Variant chr15-74411588-T-C is described in ClinVar as Benign. ClinVar VariationId is 3060979.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-1.37 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.649 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.1545A>G	p.Gln515Gln	synonymous	Exon 12 of 14	NP_003603.1	O75326-1
	SEMA7A	NM_001146029.3		c.1503A>G	p.Gln501Gln	synonymous	Exon 11 of 13	NP_001139501.1	O75326-2
	SEMA7A	NM_001146030.3		c.1050A>G	p.Gln350Gln	synonymous	Exon 12 of 14	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.1545A>G	p.Gln515Gln	synonymous	Exon 12 of 14	ENSP00000261918.4	O75326-1
	SEMA7A	ENST00000543145.6	TSL:2	c.1503A>G	p.Gln501Gln	synonymous	Exon 11 of 13	ENSP00000438966.2	O75326-2
	SEMA7A	ENST00000542748.6	TSL:5	c.1050A>G	p.Gln350Gln	synonymous	Exon 12 of 14	ENSP00000441493.1	F5GYX3

Frequencies

GnomAD3 genomes AF: 0.391 AC: 59446 AN: 151898 Hom.: 14084 Cov.: 32

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.414

Gnomad AMR AF: 0.305

Gnomad ASJ AF: 0.275

Gnomad EAS AF: 0.546

Gnomad SAS AF: 0.535

Gnomad FIN AF: 0.227

Gnomad MID AF: 0.396

Gnomad NFE AF: 0.261

Gnomad OTH AF: 0.352

GnomAD2 exomes AF: 0.347 AC: 80691 AN: 232822 AF XY: 0.346

Gnomad AFR exome AF: 0.664

Gnomad AMR exome AF: 0.324

Gnomad ASJ exome AF: 0.273

Gnomad EAS exome AF: 0.556

Gnomad FIN exome AF: 0.228

Gnomad NFE exome AF: 0.255

Gnomad OTH exome AF: 0.304

GnomAD4 exome AF: 0.295 AC: 422985 AN: 1435996 Hom.: 69657 Cov.: 36 AF XY: 0.299 AC XY: 213087 AN XY: 711824

African (AFR) AF: 0.674 AC: 22069 AN: 32762

American (AMR) AF: 0.319 AC: 13235 AN: 41452

Ashkenazi Jewish (ASJ) AF: 0.276 AC: 6707 AN: 24332

East Asian (EAS) AF: 0.516 AC: 20344 AN: 39404

South Asian (SAS) AF: 0.517 AC: 42806 AN: 82836

European-Finnish (FIN) AF: 0.225 AC: 11790 AN: 52462

Middle Eastern (MID) AF: 0.413 AC: 2195 AN: 5310

European-Non Finnish (NFE) AF: 0.259 AC: 284374 AN: 1098318

Other (OTH) AF: 0.329 AC: 19465 AN: 59120

GnomAD4 genome AF: 0.392 AC: 59562 AN: 152016 Hom.: 14129 Cov.: 32 AF XY: 0.393 AC XY: 29212 AN XY: 74304

African (AFR) AF: 0.656 AC: 27165 AN: 41420

American (AMR) AF: 0.305 AC: 4672 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.275 AC: 953 AN: 3466

East Asian (EAS) AF: 0.546 AC: 2816 AN: 5158

South Asian (SAS) AF: 0.537 AC: 2585 AN: 4818

European-Finnish (FIN) AF: 0.227 AC: 2398 AN: 10586

Middle Eastern (MID) AF: 0.408 AC: 120 AN: 294

European-Non Finnish (NFE) AF: 0.261 AC: 17725 AN: 67958

Other (OTH) AF: 0.357 AC: 753 AN: 2112

Alfa AF: 0.299 Hom.: 29739

Bravo AF: 0.406

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	SEMA7A-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	8.9
DANN	Benign	0.48
PhyloP100		-1.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs741761; hg19: chr15-74703929; COSMIC: COSV56091520; COSMIC: COSV56091520;