rs3808536

Positions:

• chr8-23290051-G-A
• chr8-23290051-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001301650.2(R3HCC1):​c.309-1G>A variant causes a splice acceptor, intron 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. 1/1 splice prediction tools predict no significant impact on normal splicing. 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_001301650.2 splice_acceptor, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_addAF=-0.570153).
• 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/exons	MANE	Protein	UniProt
R3HCC1	NM_001136108.3	c.434G>A	p.Arg145Lys	missense_variant	4/8	ENST00000265806.12	NP_001129580.2
R3HCC1	NM_001301650.2	c.309-1G>A		splice_acceptor_variant, intron_variant			NP_001288579.1
R3HCC1	NR_125897.1	n.518G>A		non_coding_transcript_exon_variant	4/9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
R3HCC1	ENST00000265806.12	c.434G>A	p.Arg145Lys	missense_variant	4/8	1	NM_001136108.3	ENSP00000265806.8

Frequencies

GnomAD3 genomes AF: 0.510 AC: 77626 AN: 152118 Hom.: 20541 Cov.: 34

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

GnomAD3 exomes AF: 0.541 AC: 79496 AN: 146850 Hom.: 22612 AF XY: 0.545 AC XY: 42940 AN XY: 78798

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 SAS exome AF: 0.537

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.: 70 AF XY: 0.560 AC XY: 385040 AN XY: 687556

Gnomad4 AFR exome AF: 0.381

Gnomad4 AMR exome AF: 0.383

Gnomad4 ASJ exome AF: 0.639

Gnomad4 EAS exome AF: 0.784

Gnomad4 SAS exome AF: 0.537

Gnomad4 FIN exome AF: 0.522

Gnomad4 NFE exome AF: 0.565

Gnomad4 OTH exome AF: 0.565

GnomAD4 genome AF: 0.510 AC: 77675 AN: 152236 Hom.: 20555 Cov.: 34 AF XY: 0.511 AC XY: 38048 AN XY: 74420

Gnomad4 AFR AF: 0.381

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.636

Gnomad4 EAS AF: 0.808

Gnomad4 SAS AF: 0.548

Gnomad4 FIN AF: 0.537

Gnomad4 NFE AF: 0.564

Gnomad4 OTH AF: 0.545

Alfa AF: 0.551 Hom.: 12094

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	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	9.9
DANN	Benign	0.92
Eigen	Benign	-0.24
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.21	N
ClinPred		0.0056	T
GERP RS		2.5

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

LitVar

Other links and lift over

dbSNP: rs3808536; hg19: chr8-23147564; COSMIC: COSV56120064; COSMIC: COSV56120064;