Genetic Variant NM_178483.3:c.255C>T (chr20-18814070-C-T) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_178483.3(SCP2D1):c.255C>T(p.Thr85Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.18 in 1,613,420 control chromosomes in the GnomAD database, including 28,873 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 0.22 ( 4640 hom., cov: 32)

Exomes 𝑓: 0.18 ( 24233 hom. )

Consequence

SCP2D1
NM_178483.3 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.435

Publications

14 publications found

Variant links:

Genes affected

SCP2D1 (HGNC:16211): (SCP2 sterol binding domain containing 1) Predicted to enable sterol binding activity. Predicted to be involved in phospholipid transport; positive regulation of intracellular cholesterol transport; and steroid biosynthetic process. [provided by Alliance of Genome Resources, Apr 2022]

SCP2D1 links:

SCP2D1-AS1 (HGNC:16210): (SCP2D1 antisense RNA 1)

SCP2D1-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP7

Synonymous conserved (PhyloP=0.435 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.378 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCP2D1	NM_178483.3 link	c.255C>T	p.Thr85Thr	synonymous_variant	Exon 1 of 1	ENST00000377428.4	NP_848578.1	Q9UJQ7
SCP2D1-AS1	NR_161342.1 link	n.269-3955G>A		intron_variant	Intron 2 of 2
SCP2D1-AS1	NR_161343.1 link	n.245-3955G>A		intron_variant	Intron 2 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCP2D1	ENST00000377428.4 link	c.255C>T	p.Thr85Thr	synonymous_variant	Exon 1 of 1	6	NM_178483.3	ENSP00000366645.2	Q9UJQ7
SCP2D1-AS1	ENST00000623418.2 link	n.273-3955G>A		intron_variant	Intron 2 of 2	2
SCP2D1-AS1	ENST00000730019.1 link	n.274+11196G>A		intron_variant	Intron 2 of 2

Frequencies

GnomAD3 genomes

AF:

0.223

AC:

33905

AN:

151988

Hom.:

4633

Cov.:

show subpopulations

Gnomad AFR

AF:

0.383

Gnomad AMI

AF:

0.0340

Gnomad AMR

AF:

0.173

Gnomad ASJ

AF:

0.162

Gnomad EAS

AF:

0.0293

Gnomad SAS

AF:

0.218

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.171

Gnomad NFE

AF:

0.164

Gnomad OTH

AF:

0.201

GnomAD2 exomes

AF:

0.175

AC:

43979

AN:

251382

AF XY:

0.176

show subpopulations

Gnomad AFR exome

AF:

0.387

Gnomad AMR exome

AF:

0.129

Gnomad ASJ exome

AF:

0.154

Gnomad EAS exome

AF:

0.0272

Gnomad FIN exome

AF:

0.194

Gnomad NFE exome

AF:

0.167

Gnomad OTH exome

AF:

0.161

GnomAD4 exome

AF:

0.176

AC:

257151

AN:

1461314

Hom.:

24233

Cov.:

AF XY:

0.177

AC XY:

128936

AN XY:

727004

show subpopulations

African (AFR)

AF:

0.386

AC:

12918

AN:

33470

American (AMR)

AF:

0.134

AC:

6015

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.151

AC:

3947

AN:

26132

East Asian (EAS)

AF:

0.0428

AC:

1699

AN:

39700

South Asian (SAS)

AF:

0.226

AC:

19524

AN:

86240

European-Finnish (FIN)

AF:

0.192

AC:

10258

AN:

53418

Middle Eastern (MID)

AF:

0.186

AC:

1070

AN:

5766

European-Non Finnish (NFE)

AF:

0.172

AC:

190652

AN:

1111486

Other (OTH)

AF:

0.183

AC:

11068

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.448

Heterozygous variant carriers

10860

21719

32579

43438

54298

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6876

13752

20628

27504

34380

<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:

0.223

AC:

33951

AN:

152106

Hom.:

4640

Cov.:

AF XY:

0.222

AC XY:

16525

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.383

AC:

15873

AN:

41460

American (AMR)

AF:

0.173

AC:

2647

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.162

AC:

561

AN:

3466

East Asian (EAS)

AF:

0.0290

AC:

150

AN:

5178

South Asian (SAS)

AF:

0.217

AC:

1044

AN:

4818

European-Finnish (FIN)

AF:

0.190

AC:

2011

AN:

10580

Middle Eastern (MID)

AF:

0.163

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.164

AC:

11166

AN:

67992

Other (OTH)

AF:

0.199

AC:

420

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1273

2547

3820

5094

6367

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

352

704

1056

1408

1760

<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:

0.179

Hom.:

4334

Bravo

AF:

0.227

Asia WGS

AF:

0.151

AC:

525

AN:

3478

EpiCase

AF:

0.169

EpiControl

AF:

0.168

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.7

(source)

DANN

Benign

0.64

PhyloP100

0.43

PromoterAI

-0.014

Neutral

(source)

Mutation Taster

=100/0

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