8-23295747-T-G

Variant names:

• chr8-23295747-T-G
• rs1002791
• NM_001136108.3:c.1193-220T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000265806.12(R3HCC1):​c.1193-220T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.304 in 609,670 control chromosomes in the GnomAD database, including 30,344 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 0.30 (7440 hom., cov: 33)
  • Exomes 𝑓: 0.30 (22904 hom.)
• Consequence: R3HCC1 ENST00000265806.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.528
• Publications: 6 publications found

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]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.597 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000265806.12. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	NM_001136108.3	MANE Select	c.1193-220T>G		intron	N/A	NP_001129580.2
	R3HCC1	NM_001301650.2		c.1067-220T>G		intron	N/A	NP_001288579.1
	R3HCC1	NR_125897.1		n.1162-220T>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	R3HCC1	ENST00000265806.12	TSL:1 MANE Select	c.1193-220T>G		intron	N/A	ENSP00000265806.8
	R3HCC1	ENST00000625275.3	TSL:1	c.1067-220T>G		intron	N/A	ENSP00000486278.2
	R3HCC1	ENST00000522012.6	TSL:1	n.*472-220T>G		intron	N/A	ENSP00000487121.2

Frequencies

GnomAD3 genomes AF: 0.302 AC: 45877 AN: 152020 Hom.: 7431 Cov.: 33

Gnomad AFR AF: 0.337

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.349

Gnomad EAS AF: 0.615

Gnomad SAS AF: 0.441

Gnomad FIN AF: 0.200

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.271

Gnomad OTH AF: 0.303

GnomAD4 exome AF: 0.304 AC: 139267 AN: 457532 Hom.: 22904 AF XY: 0.311 AC XY: 74510 AN XY: 239830

African (AFR) AF: 0.348 AC: 4332 AN: 12454

American (AMR) AF: 0.222 AC: 3898 AN: 17532

Ashkenazi Jewish (ASJ) AF: 0.350 AC: 4679 AN: 13350

East Asian (EAS) AF: 0.536 AC: 16238 AN: 30286

South Asian (SAS) AF: 0.423 AC: 18492 AN: 43734

European-Finnish (FIN) AF: 0.211 AC: 6320 AN: 29914

Middle Eastern (MID) AF: 0.285 AC: 561 AN: 1970

European-Non Finnish (NFE) AF: 0.272 AC: 76869 AN: 282440

Other (OTH) AF: 0.305 AC: 7878 AN: 25852

GnomAD4 genome AF: 0.302 AC: 45924 AN: 152138 Hom.: 7440 Cov.: 33 AF XY: 0.300 AC XY: 22344 AN XY: 74378

African (AFR) AF: 0.337 AC: 14001 AN: 41512

American (AMR) AF: 0.243 AC: 3711 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.349 AC: 1212 AN: 3468

East Asian (EAS) AF: 0.615 AC: 3174 AN: 5158

South Asian (SAS) AF: 0.441 AC: 2129 AN: 4828

European-Finnish (FIN) AF: 0.200 AC: 2124 AN: 10596

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.271 AC: 18442 AN: 67976

Other (OTH) AF: 0.308 AC: 651 AN: 2112

Alfa AF: 0.283 Hom.: 19448

Bravo AF: 0.305

Asia WGS AF: 0.467 AC: 1624 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.63
DANN	Benign	0.42
PhyloP100		-0.53
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1002791; hg19: chr8-23153260; COSMIC: COSV56120973; COSMIC: COSV56120973;