Genetic Variant NM_020151.4:c.419G>C (chr2-96195421-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020151.4(STARD7):c.419G>C(p.Arg140Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.161 in 1,610,920 control chromosomes in the GnomAD database, including 22,112 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R140C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.14 ( 1591 hom., cov: 32)

Exomes 𝑓: 0.16 ( 20521 hom. )

Consequence

STARD7
NM_020151.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.15

Publications

24 publications found

Variant links:

Genes affected

STARD7 (HGNC:18063): (StAR related lipid transfer domain containing 7) Predicted to enable lipid binding activity. Predicted to act upstream of or within several processes, including establishment of skin barrier; mucociliary clearance; and myeloid dendritic cell activation. Predicted to be located in cytoplasm and extracellular region. Implicated in familial adult myoclonic epilepsy 2. [provided by Alliance of Genome Resources, Apr 2022]

STARD7 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP4

Computational evidence support a benign effect (MetaRNN=0.0013928711).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.207 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
STARD7	NM_020151.4 link	c.419G>C	p.Arg140Pro	missense_variant	Exon 2 of 8	ENST00000337288.10	NP_064536.2	Q9NQZ5
STARD7	NM_001385622.1 link	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 8		NP_001372551.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
STARD7	ENST00000337288.10 link	c.419G>C	p.Arg140Pro	missense_variant	Exon 2 of 8	1	NM_020151.4	ENSP00000338030.5	Q9NQZ5
STARD7	ENST00000443962.1 link	c.116G>C	p.Arg39Pro	missense_variant	Exon 2 of 5	5		ENSP00000409410.1	C9JTD3
STARD7	ENST00000462501.1 link	n.94G>C		non_coding_transcript_exon_variant	Exon 1 of 7	2
STARD7	ENST00000488084.1 link	n.166G>C		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes

AF:

0.135

AC:

20563

AN:

152116

Hom.:

1585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0623

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.155

Gnomad ASJ

AF:

0.158

Gnomad EAS

AF:

0.112

Gnomad SAS

AF:

0.217

Gnomad FIN

AF:

0.141

Gnomad MID

AF:

0.177

Gnomad NFE

AF:

0.168

Gnomad OTH

AF:

0.166

GnomAD2 exomes

AF:

0.151

AC:

37184

AN:

246030

AF XY:

0.157

show subpopulations

Gnomad AFR exome

AF:

0.0585

Gnomad AMR exome

AF:

0.117

Gnomad ASJ exome

AF:

0.157

Gnomad EAS exome

AF:

0.108

Gnomad FIN exome

AF:

0.147

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.176

GnomAD4 exome

AF:

0.163

AC:

238489

AN:

1458686

Hom.:

20521

Cov.:

AF XY:

0.166

AC XY:

120597

AN XY:

725306

show subpopulations

African (AFR)

AF:

0.0636

AC:

2128

AN:

33464

American (AMR)

AF:

0.121

AC:

5350

AN:

44316

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

4111

AN:

26020

East Asian (EAS)

AF:

0.111

AC:

4410

AN:

39646

South Asian (SAS)

AF:

0.228

AC:

19486

AN:

85572

European-Finnish (FIN)

AF:

0.146

AC:

7792

AN:

53226

Middle Eastern (MID)

AF:

0.222

AC:

1276

AN:

5758

European-Non Finnish (NFE)

AF:

0.165

AC:

183759

AN:

1110400

Other (OTH)

AF:

0.169

AC:

10177

AN:

60284

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.468

Heterozygous variant carriers

10868

21735

32603

43470

54338

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6534

13068

19602

26136

32670

<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:

0.135

AC:

20590

AN:

152234

Hom.:

1591

Cov.:

AF XY:

0.137

AC XY:

10166

AN XY:

74414

show subpopulations

African (AFR)

AF:

0.0625

AC:

2597

AN:

41556

American (AMR)

AF:

0.155

AC:

2372

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.158

AC:

548

AN:

3470

East Asian (EAS)

AF:

0.111

AC:

577

AN:

5178

South Asian (SAS)

AF:

0.218

AC:

1049

AN:

4818

European-Finnish (FIN)

AF:

0.141

AC:

1498

AN:

10598

Middle Eastern (MID)

AF:

0.187

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.168

AC:

11404

AN:

68010

Other (OTH)

AF:

0.170

AC:

360

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

894

1788

2682

3576

4470

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

242

484

726

968

1210

<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:

0.149

Hom.:

1453

Bravo

AF:

0.128

TwinsUK

AF:

0.171

AC:

635

ALSPAC

AF:

0.160

AC:

615

ESP6500AA

AF:

0.0667

AC:

294

ESP6500EA

AF:

0.165

AC:

1418

ExAC

AF:

0.149

AC:

18115

Asia WGS

AF:

0.164

AC:

568

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.057

BayesDel_addAF

Benign

-0.60

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.65

DEOGEN2

Benign

0.0055

T;T

Eigen

Benign

-0.80

Eigen_PC

Benign

-0.62

FATHMM_MKL

Benign

0.14

LIST_S2

Benign

0.071

T;T

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-0.90

MutationAssessor

Benign

-0.97

N;.

PhyloP100

2.1

PrimateAI

Benign

0.45

PROVEAN

Benign

1.7

N;N

REVEL

Uncertain

0.32

Sift

Benign

1.0

T;T

Sift4G

Benign

0.77

T;.

Polyphen

0.0

B;.

Vest4

0.043

MPC

0.82

ClinPred

0.0098

GERP RS

4.7

Varity_R

0.11

gMVP

0.40

Mutation Taster

=99/1

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over