rs370782611

Variant names:

• chr14-23995055-C-G
• rs370782611
• NM_198083.4:c.330C>G

Your query was ambiguous. Multiple possible variants found:

• chr14-23995055-C-G
• chr14-23995055-C-T

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_198083.4(DHRS4L2):​c.330C>G​(p.Ile110Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000108 in 1,612,892 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I110V) has been classified as Likely benign.

• Frequency:
  • Genomes: 𝑓 0.00014 (1 hom., cov: 32)
  • Exomes 𝑓: 0.00010 (5 hom.)
• Consequence: DHRS4L2 NM_198083.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -1.21
• Publications: 2 publications found

Genes affected

DHRS4L2 (HGNC:19731): (dehydrogenase/reductase 4 like 2) This gene encodes a member of the short chain dehydrogenase reductase family. The encoded protein may be an NADPH dependent retinol oxidoreductase. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Aug 2010]

DHRS4L1 (HGNC:):

DHRS4-AS1 (HGNC:23175): (DHRS4 antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.19635937).
• BS2: High Homozygotes in GnomAdExome4 at 5 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198083.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS4L2	NM_198083.4	MANE Select	c.330C>G	p.Ile110Met	missense	Exon 3 of 8	NP_932349.2	Q6PKH6-1
	DHRS4L2	NM_001193636.1		c.27C>G	p.Ile9Met	missense	Exon 3 of 8	NP_001180565.1	A0A087WSZ6
	DHRS4L2	NM_001193637.1		c.27C>G	p.Ile9Met	missense	Exon 3 of 6	NP_001180566.1	D5KJA1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DHRS4L2	ENST00000335125.11	TSL:1 MANE Select	c.330C>G	p.Ile110Met	missense	Exon 3 of 8	ENSP00000334801.6	Q6PKH6-1
	DHRS4L2	ENST00000559387.5	TSL:5	c.-49C>G		5_prime_UTR_premature_start_codon_gain	Exon 3 of 5	ENSP00000453173.1	H0YLE1
	DHRS4L2	ENST00000559411.5	TSL:5	c.330C>G	p.Ile110Met	missense	Exon 3 of 7	ENSP00000453889.1	Q6PKH6-2

Frequencies

GnomAD3 genomes AF: 0.000138 AC: 21 AN: 151668 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000459

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.0000959

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.0000737

Gnomad OTH AF: 0.000481

GnomAD2 exomes AF: 0.000163 AC: 41 AN: 251360 AF XY: 0.000199

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000173

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.000229

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000104 AC: 152 AN: 1461106 Hom.: 5 Cov.: 31 AF XY: 0.000124 AC XY: 90 AN XY: 726828

African (AFR) AF: 0.00 AC: 0 AN: 33480

American (AMR) AF: 0.000157 AC: 7 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.000313 AC: 27 AN: 86174

European-Finnish (FIN) AF: 0.0000188 AC: 1 AN: 53222

Middle Eastern (MID) AF: 0.00330 AC: 19 AN: 5764

European-Non Finnish (NFE) AF: 0.0000774 AC: 86 AN: 1111566

Other (OTH) AF: 0.000199 AC: 12 AN: 60364

GnomAD4 genome AF: 0.000145 AC: 22 AN: 151786 Hom.: 1 Cov.: 32 AF XY: 0.000175 AC XY: 13 AN XY: 74138

African (AFR) AF: 0.0000241 AC: 1 AN: 41498

American (AMR) AF: 0.000459 AC: 7 AN: 15266

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.000629 AC: 3 AN: 4772

European-Finnish (FIN) AF: 0.0000959 AC: 1 AN: 10430

Middle Eastern (MID) AF: 0.0136 AC: 4 AN: 294

European-Non Finnish (NFE) AF: 0.0000737 AC: 5 AN: 67866

Other (OTH) AF: 0.000476 AC: 1 AN: 2102

Alfa AF: 0.000158 Hom.: 0

Bravo AF: 0.000102

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.000181 AC: 22

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.10
CADD	Benign	9.5
DANN	Benign	0.93
DEOGEN2	Benign	0.14	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.021	N
LIST_S2	Uncertain	0.93	D
M_CAP	Pathogenic	0.32	D
MetaRNN	Benign	0.20	T
MetaSVM	Uncertain	-0.26	T
PhyloP100		-1.2
PROVEAN	Benign	-2.0	N
REVEL	Uncertain	0.41
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.029	D
Vest4		0.63
MVP		0.64
MPC		0.18
ClinPred		0.11	T
GERP RS		-8.3
PromoterAI		-0.0020	Neutral
gMVP		0.48
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs370782611; hg19: chr14-24464264;