17-21191067-G-A

Position:

• chr17-21191067-G-A

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_015510.5(DHRS7B):​c.892G>A​(p.Val298Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DHRS7B NM_015510.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.247

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 Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05064714).
• BP6: Variant 17-21191067-G-A is Benign according to our data. Variant chr17-21191067-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3271822.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DHRS7B	NM_015510.5	c.892G>A	p.Val298Ile	missense_variant	7/7	ENST00000395511.8	NP_056325.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DHRS7B	ENST00000395511.8	c.892G>A	p.Val298Ile	missense_variant	7/7	1	NM_015510.5	ENSP00000378887	A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

May 26, 2024

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	0.86
DANN	Benign	0.48
DEOGEN2	Benign	0.024	T;T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.73	T;T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.66	N;.
MutationTaster	Benign	1.0	D;N;N
PrimateAI	Benign	0.28	T
PROVEAN	Benign	0.15	N;.
REVEL	Benign	0.048
Sift	Benign	1.0	T;.
Sift4G	Benign	0.94	T;T
Polyphen		0.018	B;.
Vest4		0.044
MutPred		0.36		Gain of catalytic residue at L303 (P = 0.0233);.;
MVP		0.081
MPC		0.15
ClinPred		0.075	T
GERP RS		-5.1
Varity_R		0.014
gMVP		0.21

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-21094380;