20-18814070-C-T

Variant names:

• chr20-18814070-C-T
• rs1053834
• NM_178483.3:c.255C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.435
• Publications: 14 publications found

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

ACMG classification

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	c.255C>T	p.Thr85Thr	synonymous_variant	Exon 1 of 1	ENST00000377428.4	NP_848578.1
SCP2D1-AS1	NR_161342.1	n.269-3955G>A		intron_variant	Intron 2 of 2
SCP2D1-AS1	NR_161343.1	n.245-3955G>A		intron_variant	Intron 2 of 2

Ensembl

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

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33905 AN: 151988 Hom.: 4633 Cov.: 32

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

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.: 33 AF XY: 0.177 AC XY: 128936 AN XY: 727004

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

GnomAD4 genome AF: 0.223 AC: 33951 AN: 152106 Hom.: 4640 Cov.: 32 AF XY: 0.222 AC XY: 16525 AN XY: 74364

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: 48 AN: 294

European-Non Finnish (NFE) AF: 0.164 AC: 11166 AN: 67992

Other (OTH) AF: 0.199 AC: 420 AN: 2112

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
DANN	Benign	0.64
PhyloP100		0.43
PromoterAI		-0.014	Neutral
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: rs1053834; hg19: chr20-18794714; COSMIC: COSV53856818; COSMIC: COSV53856818;