dbSNP rs3808536: R3HCC1:p.Arg145Lys (chr8-23290051-G-A) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_001136108.3(R3HCC1):c.434G>A(p.Arg145Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.556 in 1,546,262 control chromosomes in the GnomAD database, including 242,207 homozygotes. In-silico tool predicts a benign outcome for this variant. 10/12 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.51 ( 20555 hom., cov: 34)

Exomes 𝑓: 0.56 ( 221652 hom. )

Consequence

R3HCC1
NM_001136108.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

Publications

23 publications found

Variant links:

Genes affected

R3HCC1 (HGNC:27329): (R3H domain and coiled-coil containing 1) Predicted to enable nucleic acid binding activity. [provided by Alliance of Genome Resources, Apr 2022]

R3HCC1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (REVEL=0.034).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.787 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
R3HCC1	NM_001136108.3 link	c.434G>A	p.Arg145Lys	missense_variant	Exon 4 of 8	ENST00000265806.12	NP_001129580.2
R3HCC1	NR_125897.1 link	n.518G>A		non_coding_transcript_exon_variant	Exon 4 of 9
R3HCC1	NM_001301650.2 link	c.309-1G>A		splice_acceptor_variant, intron_variant	Intron 4 of 8		NP_001288579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
R3HCC1	ENST00000265806.12 link	c.434G>A	p.Arg145Lys	missense_variant	Exon 4 of 8	1	NM_001136108.3	ENSP00000265806.8

Frequencies

GnomAD3 genomes

AF:

0.510

AC:

77626

AN:

152118

Hom.:

20541

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.738

Gnomad AMR

AF:

0.444

Gnomad ASJ

AF:

0.636

Gnomad EAS

AF:

0.808

Gnomad SAS

AF:

0.548

Gnomad FIN

AF:

0.537

Gnomad MID

AF:

0.592

Gnomad NFE

AF:

0.564

Gnomad OTH

AF:

0.542

GnomAD2 exomes

AF:

0.541

AC:

79496

AN:

146850

AF XY:

0.545

show subpopulations

Gnomad AFR exome

AF:

0.381

Gnomad AMR exome

AF:

0.382

Gnomad ASJ exome

AF:

0.641

Gnomad EAS exome

AF:

0.820

Gnomad FIN exome

AF:

0.523

Gnomad NFE exome

AF:

0.567

Gnomad OTH exome

AF:

0.559

GnomAD4 exome

AF:

0.560

AC:

781345

AN:

1394026

Hom.:

221652

Cov.:

AF XY:

0.560

AC XY:

385040

AN XY:

687556

show subpopulations

African (AFR)

AF:

0.381

AC:

12034

AN:

31598

American (AMR)

AF:

0.383

AC:

13680

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.639

AC:

16087

AN:

25182

East Asian (EAS)

AF:

0.784

AC:

28011

AN:

35738

South Asian (SAS)

AF:

0.537

AC:

42543

AN:

79234

European-Finnish (FIN)

AF:

0.522

AC:

22966

AN:

43992

Middle Eastern (MID)

AF:

0.593

AC:

3379

AN:

5698

European-Non Finnish (NFE)

AF:

0.565

AC:

609909

AN:

1078920

Other (OTH)

AF:

0.565

AC:

32736

AN:

57962

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.484

Heterozygous variant carriers

22204

44408

66611

88815

111019

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

17238

34476

51714

68952

86190

<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:

0.510

AC:

77675

AN:

152236

Hom.:

20555

Cov.:

AF XY:

0.511

AC XY:

38048

AN XY:

74420

show subpopulations

African (AFR)

AF:

0.381

AC:

15814

AN:

41534

American (AMR)

AF:

0.444

AC:

6784

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.636

AC:

2207

AN:

3470

East Asian (EAS)

AF:

0.808

AC:

4182

AN:

5178

South Asian (SAS)

AF:

0.548

AC:

2649

AN:

4832

European-Finnish (FIN)

AF:

0.537

AC:

5692

AN:

10602

Middle Eastern (MID)

AF:

0.599

AC:

176

AN:

294

European-Non Finnish (NFE)

AF:

0.564

AC:

38346

AN:

68006

Other (OTH)

AF:

0.545

AC:

1152

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

2010

4019

6029

8038

10048

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

688

1376

2064

2752

3440

<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:

0.550

Hom.:

43729

Bravo

AF:

0.500

TwinsUK

AF:

0.574

AC:

2130

ALSPAC

AF:

0.565

AC:

2178

ExAC

AF:

0.485

AC:

11608

Asia WGS

AF:

0.636

AC:

2210

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.091

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.69

CADD

Benign

9.9

(source)

DANN

Benign

0.92

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.28

FATHMM_MKL

Benign

0.21

PhyloP100

0.36

ClinPred

0.0056

GERP RS

2.5

PromoterAI

0.034

Neutral

(source)

Mutation Taster

=68/32

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over