rs4459983

Variant names:

• chr4-82649098-A-G
• rs4459983
• NM_001037582.3:c.570-12275T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-82649098-A-G
• chr4-82649098-A-T

Variant summary

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

The NM_001037582.3(SCD5):​c.570-12275T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.759 in 151,404 control chromosomes in the GnomAD database, including 44,463 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 0.76 (44463 hom., cov: 28)
• Consequence: SCD5 NM_001037582.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.699
• Publications: 3 publications found

Genes affected

SCD5 (HGNC:21088): (stearoyl-CoA desaturase 5) Stearoyl-CoA desaturase (SCD; EC 1.14.99.5) is an integral membrane protein of the endoplasmic reticulum that catalyzes the formation of monounsaturated fatty acids from saturated fatty acids. SCD may be a key regulator of energy metabolism with a role in obesity and dislipidemia. Four SCD isoforms, Scd1 through Scd4, have been identified in mouse. In contrast, only 2 SCD isoforms, SCD1 (MIM 604031) and SCD5, have been identified in human. SCD1 shares about 85% amino acid identity with all 4 mouse SCD isoforms, as well as with rat Scd1 and Scd2. In contrast, SCD5 shares limited homology with the rodent SCDs and appears to be unique to primates (Wang et al., 2005 [PubMed 15907797]).[supplied by OMIM, Mar 2008]

SCD5 Gene-Disease associations (from GenCC):

• hearing loss, autosomal dominant 79

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.97 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCD5	NM_001037582.3	c.570-12275T>C		intron_variant	Intron 3 of 4	ENST00000319540.9	NP_001032671.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCD5	ENST00000319540.9	c.570-12275T>C		intron_variant	Intron 3 of 4	1	NM_001037582.3	ENSP00000316329.4

Frequencies

GnomAD3 genomes AF: 0.759 AC: 114835 AN: 151288 Hom.: 44442 Cov.: 28

Gnomad AFR AF: 0.598

Gnomad AMI AF: 0.708

Gnomad AMR AF: 0.838

Gnomad ASJ AF: 0.761

Gnomad EAS AF: 0.993

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.775

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.823

Gnomad OTH AF: 0.778

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

GnomAD4 genome AF: 0.759 AC: 114895 AN: 151404 Hom.: 44463 Cov.: 28 AF XY: 0.757 AC XY: 55937 AN XY: 73886

African (AFR) AF: 0.598 AC: 24606 AN: 41168

American (AMR) AF: 0.838 AC: 12745 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.761 AC: 2642 AN: 3470

East Asian (EAS) AF: 0.993 AC: 5125 AN: 5162

South Asian (SAS) AF: 0.701 AC: 3347 AN: 4776

European-Finnish (FIN) AF: 0.775 AC: 8055 AN: 10400

Middle Eastern (MID) AF: 0.752 AC: 221 AN: 294

European-Non Finnish (NFE) AF: 0.823 AC: 55872 AN: 67924

Other (OTH) AF: 0.780 AC: 1642 AN: 2106

Alfa AF: 0.798 Hom.: 28504

Bravo AF: 0.761

Asia WGS AF: 0.843 AC: 2934 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.087
DANN	Benign	0.67
PhyloP100		-0.70
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: rs4459983; hg19: chr4-83570251;