Genetic Variant DHRS7C:c.268-12T>C (chr17-9780047-A-G) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_001105571.3(DHRS7C):c.268-12T>C variant causes a intron change. The variant allele was found at a frequency of 0.00059 in 1,612,208 control chromosomes in the GnomAD database, including 14 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00079 ( 4 hom., cov: 32)

Exomes 𝑓: 0.00057 ( 10 hom. )

Consequence

DHRS7C
NM_001105571.3 intron

Scores

Splicing: ADA: 0.2602

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.75

Variant links:

Genes affected

DHRS7C (HGNC:32423): (dehydrogenase/reductase 7C) Predicted to enable NAD-retinol dehydrogenase activity. Predicted to be involved in regulation of release of sequestered calcium ion into cytosol by sarcoplasmic reticulum. Predicted to be located in extracellular region and longitudinal sarcoplasmic reticulum. Predicted to be active in sarcoplasmic reticulum membrane. [provided by Alliance of Genome Resources, Apr 2022]

DHRS7C links:

ENSG00000282882 (HGNC:):

ENSG00000282882 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.47).

BP6

Variant 17-9780047-A-G is Benign according to our data. Variant chr17-9780047-A-G is described in ClinVar as [Benign]. Clinvar id is 735107.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.000795 (121/152238) while in subpopulation EAS AF= 0.0196 (101/5164). AF 95% confidence interval is 0.0165. There are 4 homozygotes in gnomad4. There are 72 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DHRS7C	NM_001105571.3 link	c.268-12T>C		intron_variant	Intron 2 of 5	ENST00000571134.2	NP_001099041.1	A6NNS2-2
DHRS7C	NM_001220493.2 link	c.268-9T>C		intron_variant	Intron 2 of 5		NP_001207422.1	A6NNS2-1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
DHRS7C	ENST00000571134.2 link	c.268-12T>C	intron_variant	Intron 2 of 5	1	NM_001105571.3	ENSP00000459579.1	A6NNS2-2
DHRS7C	ENST00000330255.9 link	c.268-9T>C	intron_variant	Intron 2 of 5	1		ENSP00000327975.4	A6NNS2-1
ENSG00000282882	ENST00000634974.2 link	n.147-2872A>G	intron_variant	Intron 1 of 3	5
DHRS7C	ENST00000571771.5 link	c.-126T>C	upstream_gene_variant		3		ENSP00000461902.2	I3NI52

Frequencies

GnomAD3 genomes

AF:

0.000802

AC:

122

AN:

152118

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.0195

Gnomad SAS

AF:

0.00124

Gnomad FIN

AF:

0.0000941

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000176

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00152

AC:

373

AN:

245960

Hom.:

AF XY:

0.00144

AC XY:

192

AN XY:

133346

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000293

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0195

Gnomad SAS exome

AF:

0.000334

Gnomad FIN exome

AF:

0.000140

Gnomad NFE exome

AF:

0.0000717

Gnomad OTH exome

AF:

0.000670

GnomAD4 exome

AF:

0.000569

AC:

831

AN:

1459970

Hom.:

Cov.:

AF XY:

0.000600

AC XY:

436

AN XY:

726068

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0171

Gnomad4 SAS exome

AF:

0.000501

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.0000675

Gnomad4 OTH exome

AF:

0.000415

GnomAD4 genome

AF:

0.000795

AC:

121

AN:

152238

Hom.:

Cov.:

AF XY:

0.000967

AC XY:

AN XY:

74434

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.0196

Gnomad4 SAS

AF:

0.00104

Gnomad4 FIN

AF:

0.0000941

Gnomad4 NFE

AF:

0.000176

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000212

Hom.:

Bravo

AF:

0.000982

Asia WGS

AF:

0.00664

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Mar 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.47

CADD

Benign

DANN

Benign

0.82

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.26

SpliceAI score (max)

0.080

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