Variant 17-21188714-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_015510.5(DHRS7B):c.623C>G(p.Ala208Gly) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000252 in 1,585,904 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000024 ( 0 hom. )

Consequence

DHRS7B
NM_015510.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.58

Variant links:

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]

DHRS7B links:

DHRS7B (HGNC:):

DHRS7B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.892

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7B	NM_015510.5 linkuse as main transcript	c.623C>G	p.Ala208Gly	missense_variant	6/7	ENST00000395511.8	NP_056325.2	Q6IAN0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7B	ENST00000395511.8 linkuse as main transcript	c.623C>G	p.Ala208Gly	missense_variant	6/7	1	NM_015510.5	ENSP00000378887.3		Q6IAN0

Frequencies

GnomAD3 genomes

AF:

0.0000395

AC:

AN:

151844

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000883

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000174

AC:

AN:

229856

Hom.:

AF XY:

0.0000324

AC XY:

AN XY:

123390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000382

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000237

AC:

AN:

1434060

Hom.:

Cov.:

AF XY:

0.0000225

AC XY:

AN XY:

710932

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000301

Gnomad4 OTH exome

AF:

0.0000169

GnomAD4 genome

AF:

0.0000395

AC:

AN:

151844

Hom.:

Cov.:

AF XY:

0.0000405

AC XY:

AN XY:

74156

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000883

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000605

Hom.:

Bravo

AF:

0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 09, 2024

The c.623C>G (p.A208G) alteration is located in exon 6 (coding exon 6) of the DHRS7B gene. This alteration results from a C to G substitution at nucleotide position 623, causing the alanine (A) at amino acid position 208 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.037

BayesDel_noAF

Uncertain

-0.070

CADD

Uncertain

DANN

Benign

0.85

DEOGEN2

Uncertain

0.53

D;T;.

Eigen

Uncertain

0.36

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.91

D;D;D

M_CAP

Uncertain

0.091

MetaRNN

Pathogenic

0.89

D;D;D

MetaSVM

Uncertain

0.48

MutationAssessor

Benign

-0.32

N;.;.

PrimateAI

Uncertain

0.64

PROVEAN

Uncertain

-2.9

D;.;.

REVEL

Pathogenic

0.66

Sift

Benign

0.072

T;.;.

Sift4G

Uncertain

0.037

D;D;D

Polyphen

0.91

P;.;.

Vest4

0.69

MutPred

0.86

Gain of methylation at K211 (P = 0.1075);.;.;

MVP

0.87

MPC

0.31

ClinPred

0.42

GERP RS

5.3

Varity_R

0.30

gMVP

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over