rs1448

Positions:

• chr17-21185027-T-C

Variant summary

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

The NM_015510.5(DHRS7B):​c.619+564T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.318 in 152,078 control chromosomes in the GnomAD database, including 7,768 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 0.32 (7768 hom., cov: 33)
• Consequence: DHRS7B NM_015510.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.772

Genes affected

DHRS7B (HGNC:24547): (dehydrogenase/reductase 7B) Predicted to enable DNA-binding transcription factor binding activity and transcription corepressor activity. Predicted to be involved in neutrophil differentiation. Predicted to act upstream of or within several processes, including brown fat cell differentiation; phosphatidylcholine biosynthetic process; and regulation of cold-induced thermogenesis. Located in membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7B	NM_015510.5	c.619+564T>C		intron_variant		ENST00000395511.8	NP_056325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7B	ENST00000395511.8	c.619+564T>C		intron_variant		1	NM_015510.5	ENSP00000378887	A1

Frequencies

GnomAD3 genomes AF: 0.318 AC: 48280 AN: 151960 Hom.: 7765 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.315

Gnomad AMR AF: 0.323

Gnomad ASJ AF: 0.246

Gnomad EAS AF: 0.274

Gnomad SAS AF: 0.364

Gnomad FIN AF: 0.338

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.328

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

GnomAD4 genome AF: 0.318 AC: 48308 AN: 152078 Hom.: 7768 Cov.: 33 AF XY: 0.316 AC XY: 23496 AN XY: 74342

Gnomad4 AFR AF: 0.269

Gnomad4 AMR AF: 0.324

Gnomad4 ASJ AF: 0.246

Gnomad4 EAS AF: 0.275

Gnomad4 SAS AF: 0.365

Gnomad4 FIN AF: 0.338

Gnomad4 NFE AF: 0.346

Gnomad4 OTH AF: 0.328

Alfa AF: 0.317 Hom.: 1310

Bravo AF: 0.312

Asia WGS AF: 0.311 AC: 1082 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.0
DANN	Benign	0.87

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: rs1448; hg19: chr17-21088340;