Variant 17-21183598-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PVS1_StrongPM2

The NM_001393657.1(DHRS7B):c.310-2A>G variant causes a splice acceptor, intron change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

DHRS7B
NM_001393657.1 splice_acceptor, intron

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.35

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 Likely_pathogenic. Variant got 6 ACMG points.

PVS1

Splicing +-2 bp (donor or acceptor) variant, product NOT destroyed by NMD, known LOF gene, truncates exone, which is 0.21604939 fraction of the gene. Cryptic splice site detected, with MaxEntScore 8, offset of -6, new splice context is: tatctgttgtatttgaccAGgtg. Cryptic site results in inframe change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7B	NM_015510.5 linkuse as main transcript	c.314A>G	p.Gln105Arg	missense_variant	4/7	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.314A>G	p.Gln105Arg	missense_variant	4/7	1	NM_015510.5	ENSP00000378887.3		Q6IAN0

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251298

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135812

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000289

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.85e-7

AC:

AN:

1460444

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

726552

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

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:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Nov 09, 2024

The c.314A>G (p.Q105R) alteration is located in exon 4 (coding exon 4) of the DHRS7B gene. This alteration results from a A to G substitution at nucleotide position 314, causing the glutamine (Q) at amino acid position 105 to be replaced by an arginine (R). 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

0.086

BayesDel_addAF

Uncertain

0.050

BayesDel_noAF

Uncertain

-0.080

CADD

Benign

DANN

Benign

0.88

DEOGEN2

Benign

0.23

.;T;T

Eigen

Benign

-0.13

Eigen_PC

Benign

0.13

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.59

T;T;T

M_CAP

Benign

0.032

MetaRNN

Benign

0.26

T;T;T

MetaSVM

Benign

-0.51

MutationAssessor

Benign

0.73

.;N;.

PrimateAI

Benign

0.42

PROVEAN

Benign

-1.2

.;N;.

REVEL

Uncertain

0.34

Sift

Benign

0.51

.;T;.

Sift4G

Benign

0.30

T;T;T

Polyphen

0.013

.;B;.

Vest4

0.55, 0.53

MutPred

0.41

Loss of ubiquitination at K108 (P = 0.074);Loss of ubiquitination at K108 (P = 0.074);.;

MVP

0.45

MPC

0.21

ClinPred

0.27

GERP RS

5.6

Varity_R

0.16

gMVP

0.55

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