Genetic Variant SCD:c.*1497C>G (chr10-100362430-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_005063.5(SCD):c.*1497C>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.234 in 152,018 control chromosomes in the GnomAD database, including 4,893 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 0.23 ( 4893 hom., cov: 32)

Exomes 𝑓: 0.14 ( 0 hom. )

Consequence

SCD
NM_005063.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.727

Publications

12 publications found

Variant links:

Genes affected

SCD (HGNC:10571): (stearoyl-CoA desaturase) This gene encodes an enzyme involved in fatty acid biosynthesis, primarily the synthesis of oleic acid. The protein belongs to the fatty acid desaturase family and is an integral membrane protein located in the endoplasmic reticulum. Transcripts of approximately 3.9 and 5.2 kb, differing only by alternative polyadenlyation signals, have been detected. A gene encoding a similar enzyme is located on chromosome 4 and a pseudogene of this gene is located on chromosome 17. [provided by RefSeq, Sep 2015]

SCD 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 (BayesDel_noAF=-0.8).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCD	NM_005063.5 link	c.*1497C>G		3_prime_UTR_variant	Exon 6 of 6	ENST00000370355.3	NP_005054.3	O00767

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3 link	c.*1497C>G		3_prime_UTR_variant	Exon 6 of 6	1	NM_005063.5	ENSP00000359380.2		O00767

Frequencies

GnomAD3 genomes

AF:

0.234

AC:

35544

AN:

151886

Hom.:

4863

Cov.:

show subpopulations

Gnomad AFR

AF:

0.365

Gnomad AMI

AF:

0.117

Gnomad AMR

AF:

0.156

Gnomad ASJ

AF:

0.217

Gnomad EAS

AF:

0.239

Gnomad SAS

AF:

0.319

Gnomad FIN

AF:

0.182

Gnomad MID

AF:

0.250

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.209

GnomAD4 exome

AF:

0.143

AC:

AN:

Hom.:

Cov.:

AF XY:

0.200

AC XY:

AN XY:

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.167

AC:

AN:

Other (OTH)

AF:

0.00

AC:

AN:

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.234

AC:

35615

AN:

152004

Hom.:

4893

Cov.:

AF XY:

0.235

AC XY:

17475

AN XY:

74288

show subpopulations

African (AFR)

AF:

0.366

AC:

15172

AN:

41428

American (AMR)

AF:

0.156

AC:

2386

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

753

AN:

3472

East Asian (EAS)

AF:

0.238

AC:

1232

AN:

5166

South Asian (SAS)

AF:

0.317

AC:

1526

AN:

4812

European-Finnish (FIN)

AF:

0.182

AC:

1923

AN:

10550

Middle Eastern (MID)

AF:

0.255

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.176

AC:

11997

AN:

67972

Other (OTH)

AF:

0.210

AC:

444

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1291

2581

3872

5162

6453

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

378

756

1134

1512

1890

<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:

0.206

Hom.:

447

Bravo

AF:

0.234

Asia WGS

AF:

0.294

AC:

1025

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

5.1

(source)

DANN

Benign

0.56

PhyloP100

0.73

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over