rs11190480

Positions:

• chr10-100352318-A-G

Variant summary

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

The NM_005063.5(SCD):​c.311-48A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0976 in 1,590,678 control chromosomes in the GnomAD database, including 8,050 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 0.091 (682 hom., cov: 32)
  • Exomes 𝑓: 0.098 (7368 hom.)
• Consequence: SCD NM_005063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.559

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=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCD	NM_005063.5	c.311-48A>G		intron_variant		ENST00000370355.3	NP_005054.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCD	ENST00000370355.3	c.311-48A>G		intron_variant		1	NM_005063.5	ENSP00000359380.2

Frequencies

GnomAD3 genomes AF: 0.0912 AC: 13874 AN: 152062 Hom.: 685 Cov.: 32

Gnomad AFR AF: 0.0867

Gnomad AMI AF: 0.0835

Gnomad AMR AF: 0.0660

Gnomad ASJ AF: 0.108

Gnomad EAS AF: 0.155

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.0807

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0935

Gnomad OTH AF: 0.0837

GnomAD3 exomes AF: 0.0934 AC: 22735 AN: 243366 Hom.: 1180 AF XY: 0.0966 AC XY: 12711 AN XY: 131622

Gnomad AFR exome AF: 0.0890

Gnomad AMR exome AF: 0.0454

Gnomad ASJ exome AF: 0.120

Gnomad EAS exome AF: 0.151

Gnomad SAS exome AF: 0.123

Gnomad FIN exome AF: 0.0754

Gnomad NFE exome AF: 0.0925

Gnomad OTH exome AF: 0.0870

GnomAD4 exome AF: 0.0983 AC: 141415 AN: 1438498 Hom.: 7368 Cov.: 28 AF XY: 0.0989 AC XY: 70562 AN XY: 713690

Gnomad4 AFR exome AF: 0.0883

Gnomad4 AMR exome AF: 0.0479

Gnomad4 ASJ exome AF: 0.120

Gnomad4 EAS exome AF: 0.151

Gnomad4 SAS exome AF: 0.124

Gnomad4 FIN exome AF: 0.0752

Gnomad4 NFE exome AF: 0.0972

Gnomad4 OTH exome AF: 0.101

GnomAD4 genome AF: 0.0912 AC: 13877 AN: 152180 Hom.: 682 Cov.: 32 AF XY: 0.0906 AC XY: 6737 AN XY: 74400

Gnomad4 AFR AF: 0.0867

Gnomad4 AMR AF: 0.0659

Gnomad4 ASJ AF: 0.108

Gnomad4 EAS AF: 0.155

Gnomad4 SAS AF: 0.123

Gnomad4 FIN AF: 0.0807

Gnomad4 NFE AF: 0.0935

Gnomad4 OTH AF: 0.0837

Alfa AF: 0.0942 Hom.: 214

Bravo AF: 0.0896

Asia WGS AF: 0.117 AC: 408 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.5
DANN	Benign	0.62
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11190480; hg19: chr10-102112075;