rs6588537

Variant names:

• chr1-54888520-G-A
• rs6588537
• ENST00000433690.1:n.73G>A

Variant summary

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

The ENST00000433690.1(DHCR24-DT):​n.73G>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0889 in 152,230 control chromosomes in the GnomAD database, including 692 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 0.089 (692 hom., cov: 32)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DHCR24-DT ENST00000433690.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.294
• Publications: 4 publications found

Genes affected

DHCR24-DT (HGNC:53969): (DHCR24 divergent transcript)

TMEM61 (HGNC:27296): (transmembrane protein 61) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.105 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHCR24-DT	XR_001738059.3	n.1010G>A		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DHCR24-DT	ENST00000433690.1	n.73G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
DHCR24-DT	ENST00000436033.1	n.271G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2
DHCR24-DT	ENST00000443284.2	n.439G>A		non_coding_transcript_exon_variant	Exon 2 of 2	2

Frequencies

GnomAD3 genomes AF: 0.0889 AC: 13524 AN: 152112 Hom.: 689 Cov.: 32

Gnomad AFR AF: 0.0689

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.0694

Gnomad EAS AF: 0.0109

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0761

Gnomad MID AF: 0.0759

Gnomad NFE AF: 0.107

Gnomad OTH AF: 0.0769

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 6 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.0889 AC: 13534 AN: 152230 Hom.: 692 Cov.: 32 AF XY: 0.0862 AC XY: 6418 AN XY: 74444

African (AFR) AF: 0.0688 AC: 2855 AN: 41526

American (AMR) AF: 0.110 AC: 1679 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0694 AC: 241 AN: 3472

East Asian (EAS) AF: 0.0110 AC: 57 AN: 5194

South Asian (SAS) AF: 0.0696 AC: 336 AN: 4828

European-Finnish (FIN) AF: 0.0761 AC: 806 AN: 10594

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.107 AC: 7306 AN: 68008

Other (OTH) AF: 0.0770 AC: 163 AN: 2116

Alfa AF: 0.0993 Hom.: 129

Bravo AF: 0.0930

Asia WGS AF: 0.0470 AC: 165 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	13
DANN	Benign	0.72
PhyloP100		0.29

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs6588537; hg19: chr1-55354193;