15-74417376-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_003612.5(SEMA7A):c.620G>A(p.Arg207Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000493 in 1,613,916 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Affects (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R207W) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 1 hom. )

Consequence

SEMA7A
NM_003612.5 missense

Scores

Clinical Significance

Affects no assertion criteria provided O:1

Conservation

PhyloP100: -0.145

Publications

10 publications found

Variant links:

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

SEMA7A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.029116422).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA7A	NM_003612.5	MANE Select	c.620G>A	p.Arg207Gln	missense	Exon 6 of 14	NP_003603.1	O75326-1
SEMA7A	NM_001146029.3		c.578G>A	p.Arg193Gln	missense	Exon 5 of 13	NP_001139501.1	O75326-2
SEMA7A	NM_001146030.3		c.125G>A	p.Arg42Gln	missense	Exon 6 of 14	NP_001139502.1	F5GYX3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SEMA7A	ENST00000261918.9	TSL:1 MANE Select	c.620G>A	p.Arg207Gln	missense	Exon 6 of 14	ENSP00000261918.4	O75326-1
SEMA7A	ENST00000543145.6	TSL:2	c.578G>A	p.Arg193Gln	missense	Exon 5 of 13	ENSP00000438966.2	O75326-2
SEMA7A	ENST00000542748.6	TSL:5	c.125G>A	p.Arg42Gln	missense	Exon 6 of 14	ENSP00000441493.1	F5GYX3

Frequencies

GnomAD3 genomes

AF:

0.000315

AC:

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000145

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000573

Gnomad OTH

AF:

0.000956

GnomAD2 exomes

AF:

0.000334

AC:

AN:

251408

AF XY:

0.000375

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000484

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000512

AC:

748

AN:

1461700

Hom.:

Cov.:

AF XY:

0.000491

AC XY:

357

AN XY:

727162

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33478

American (AMR)

AF:

0.0000447

AC:

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39698

South Asian (SAS)

AF:

0.000719

AC:

AN:

86256

European-Finnish (FIN)

AF:

0.0000188

AC:

AN:

53280

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.000596

AC:

663

AN:

1111974

Other (OTH)

AF:

0.000232

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

116

155

194

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

130

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000315

AC:

AN:

152216

Hom.:

Cov.:

AF XY:

0.000269

AC XY:

AN XY:

74360

show subpopulations

African (AFR)

AF:

0.000145

AC:

AN:

41442

American (AMR)

AF:

0.0000655

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10628

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.000573

AC:

AN:

68042

Other (OTH)

AF:

0.000956

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.000499

Hom.:

Bravo

AF:

0.000359

TwinsUK

AF:

0.000539

AC:

ALSPAC

AF:

0.000519

AC:

ESP6500AA

AF:

0.000228

AC:

ESP6500EA

AF:

0.000815

AC:

ExAC

AF:

0.000346

AC:

EpiCase

AF:

0.000491

EpiControl

AF:

0.000830

ClinVar

ClinVar submissions

Significance:Affects

Revision:no assertion criteria provided

View on ClinVar

Pathogenic

VUS

Benign

Condition

John Milton Hagen blood group system (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.062

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.50

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.059

Eigen

Benign

-1.2

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.065

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.15

MetaRNN

Benign

0.029

MetaSVM

Benign

-0.92

MutationAssessor

Benign

-0.23

PhyloP100

-0.14

PrimateAI

Benign

0.23

PROVEAN

Benign

0.28

REVEL

Benign

0.28

Sift

Benign

0.56

Sift4G

Benign

0.43

Polyphen

0.0050

Vest4

0.17

MVP

0.29

MPC

0.53

ClinPred

0.017

GERP RS

-1.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.13

gMVP

0.43

Mutation Taster

=85/15

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over