rs3071

Positions:

• chr10-100354706-A-C
• chr10-100354706-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005063.5(SCD):​c.647+74A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.288 in 1,149,876 control chromosomes in the GnomAD database, including 50,783 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 0.24 (5535 hom., cov: 32)
  • Exomes 𝑓: 0.29 (45248 hom.)
• Consequence: SCD NM_005063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.365

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.323 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCD	NM_005063.5	c.647+74A>C		intron_variant		ENST00000370355.3	NP_005054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3	c.647+74A>C		intron_variant		1	NM_005063.5	ENSP00000359380	P1

Frequencies

GnomAD3 genomes AF: 0.240 AC: 36498 AN: 151952 Hom.: 5537 Cov.: 32

Gnomad AFR AF: 0.0557

Gnomad AMI AF: 0.375

Gnomad AMR AF: 0.264

Gnomad ASJ AF: 0.241

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.301

Gnomad FIN AF: 0.403

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.246

GnomAD4 exome AF: 0.295 AC: 294261 AN: 997804 Hom.: 45248 AF XY: 0.296 AC XY: 150769 AN XY: 509052

Gnomad4 AFR exome AF: 0.0470

Gnomad4 AMR exome AF: 0.263

Gnomad4 ASJ exome AF: 0.235

Gnomad4 EAS exome AF: 0.300

Gnomad4 SAS exome AF: 0.297

Gnomad4 FIN exome AF: 0.399

Gnomad4 NFE exome AF: 0.301

Gnomad4 OTH exome AF: 0.273

GnomAD4 genome AF: 0.240 AC: 36496 AN: 152072 Hom.: 5535 Cov.: 32 AF XY: 0.247 AC XY: 18362 AN XY: 74330

Gnomad4 AFR AF: 0.0556

Gnomad4 AMR AF: 0.264

Gnomad4 ASJ AF: 0.241

Gnomad4 EAS AF: 0.336

Gnomad4 SAS AF: 0.302

Gnomad4 FIN AF: 0.403

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.246

Alfa AF: 0.208 Hom.: 1057

Bravo AF: 0.218

Asia WGS AF: 0.307 AC: 1066 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.8
DANN	Benign	0.47
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

LitVar

Other links and lift over

dbSNP: rs3071; hg19: chr10-102114463;