Genetic Variant R3HDML:c.262-38A>G (chr20-44341158-A-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_178491.4(R3HDML):c.262-38A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.178 in 1,537,372 control chromosomes in the GnomAD database, including 27,719 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.18 ( 2765 hom., cov: 33)

Exomes 𝑓: 0.18 ( 24954 hom. )

Consequence

R3HDML
NM_178491.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.77

Publications

14 publications found

Variant links:

Genes affected

R3HDML (HGNC:16249): (R3H domain containing like) Predicted to enable peptidase inhibitor activity. Predicted to be involved in negative regulation of peptidase activity. Predicted to be active in extracellular space. [provided by Alliance of Genome Resources, Apr 2022]

R3HDML links:

R3HDML-AS1 (HGNC:55830): (R3HDML antisense RNA 1)

R3HDML-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.359 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_178491.4. 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
	R3HDML	NM_178491.4	MANE Select	c.262-38A>G		intron	N/A	NP_848586.1	Q9H3Y0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HDML	ENST00000217043.4	TSL:1 MANE Select	c.262-38A>G		intron	N/A	ENSP00000217043.3	Q9H3Y0
	R3HDML-AS1	ENST00000735551.1		n.601-2098T>C		intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.176

AC:

26830

AN:

152112

Hom.:

2746

Cov.:

show subpopulations

Gnomad AFR

AF:

0.133

Gnomad AMI

AF:

0.162

Gnomad AMR

AF:

0.295

Gnomad ASJ

AF:

0.208

Gnomad EAS

AF:

0.372

Gnomad SAS

AF:

0.261

Gnomad FIN

AF:

0.118

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.163

Gnomad OTH

AF:

0.170

GnomAD2 exomes

AF:

0.218

AC:

52111

AN:

239062

AF XY:

0.213

show subpopulations

Gnomad AFR exome

AF:

0.128

Gnomad AMR exome

AF:

0.401

Gnomad ASJ exome

AF:

0.202

Gnomad EAS exome

AF:

0.380

Gnomad FIN exome

AF:

0.122

Gnomad NFE exome

AF:

0.161

Gnomad OTH exome

AF:

0.202

GnomAD4 exome

AF:

0.178

AC:

247030

AN:

1385142

Hom.:

24954

Cov.:

AF XY:

0.180

AC XY:

123735

AN XY:

688460

show subpopulations

African (AFR)

AF:

0.122

AC:

3916

AN:

32022

American (AMR)

AF:

0.383

AC:

16283

AN:

42494

Ashkenazi Jewish (ASJ)

AF:

0.199

AC:

4906

AN:

24610

East Asian (EAS)

AF:

0.387

AC:

15076

AN:

38940

South Asian (SAS)

AF:

0.242

AC:

20066

AN:

82852

European-Finnish (FIN)

AF:

0.122

AC:

6422

AN:

52786

Middle Eastern (MID)

AF:

0.166

AC:

856

AN:

5154

European-Non Finnish (NFE)

AF:

0.161

AC:

169051

AN:

1048814

Other (OTH)

AF:

0.182

AC:

10454

AN:

57470

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

9696

19392

29089

38785

48481

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6238

12476

18714

24952

31190

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.177

AC:

26878

AN:

152230

Hom.:

2765

Cov.:

AF XY:

0.180

AC XY:

13383

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.133

AC:

5522

AN:

41576

American (AMR)

AF:

0.297

AC:

4531

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.208

AC:

723

AN:

3472

East Asian (EAS)

AF:

0.373

AC:

1920

AN:

5146

South Asian (SAS)

AF:

0.261

AC:

1262

AN:

4828

European-Finnish (FIN)

AF:

0.118

AC:

1253

AN:

10608

Middle Eastern (MID)

AF:

0.184

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.163

AC:

11098

AN:

68012

Other (OTH)

AF:

0.175

AC:

368

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1151

2302

3452

4603

5754

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

296

592

888

1184

1480

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.156

Hom.:

1137

Bravo

AF:

0.187

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.17

(source)

DANN

Benign

0.71

PhyloP100

-1.8

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over