rs681278

Variant names:

• chr10-100351289-A-G
• rs681278
• NM_005063.5:c.311-1077A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_005063.5(SCD):​c.311-1077A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0387 in 152,192 control chromosomes in the GnomAD database, including 238 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 0.039 (238 hom., cov: 32)
• Consequence: SCD NM_005063.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.134
• Publications: 2 publications found

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 Gene-Disease associations (from GenCC):

• adrenoleukodystrophy

  Inheritance: AR Classification: LIMITED Submitted by: PanelApp Australia

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005063.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	NM_005063.5	MANE Select	c.311-1077A>G		intron	N/A	NP_005054.3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCD	ENST00000370355.3	TSL:1 MANE Select	c.311-1077A>G		intron	N/A	ENSP00000359380.2	O00767
	SCD	ENST00000884321.1		c.446-1077A>G		intron	N/A	ENSP00000554380.1
	SCD	ENST00000884322.1		c.368-1077A>G		intron	N/A	ENSP00000554381.1

Frequencies

GnomAD3 genomes AF: 0.0386 AC: 5877 AN: 152074 Hom.: 239 Cov.: 32

Gnomad AFR AF: 0.0877

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0266

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.121

Gnomad SAS AF: 0.0711

Gnomad FIN AF: 0.0431

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00510

Gnomad OTH AF: 0.0268

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0387 AC: 5889 AN: 152192 Hom.: 238 Cov.: 32 AF XY: 0.0413 AC XY: 3073 AN XY: 74420

African (AFR) AF: 0.0877 AC: 3642 AN: 41506

American (AMR) AF: 0.0265 AC: 406 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.121 AC: 622 AN: 5152

South Asian (SAS) AF: 0.0705 AC: 340 AN: 4820

European-Finnish (FIN) AF: 0.0431 AC: 458 AN: 10616

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.00510 AC: 347 AN: 68018

Other (OTH) AF: 0.0289 AC: 61 AN: 2108

Alfa AF: 0.0143 Hom.: 84

Bravo AF: 0.0393

Asia WGS AF: 0.118 AC: 412 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.7
DANN	Benign	0.71
PhyloP100		-0.13
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: rs681278; hg19: chr10-102111046;