17-5432432-C-T

Variant names:

• chr17-5432432-C-T
• rs8072363
• NM_001033002.4:c.631-110C>T

Variant summary

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

The NM_001033002.4(RPAIN):​c.631-110C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 1,011,576 control chromosomes in the GnomAD database, including 46,661 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 0.24 (5694 hom., cov: 32)
  • Exomes 𝑓: 0.28 (40967 hom.)
• Consequence: RPAIN NM_001033002.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.116
• Publications: 21 publications found

Genes affected

RPAIN (HGNC:28641): (RPA interacting protein) Predicted to enable metal ion binding activity. Acts upstream of or within several processes, including DNA metabolic process; protein import into nucleus; and response to UV. Located in PML body; cytoplasm; and fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000263272 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.779 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001033002.4. 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
	RPAIN	NM_001033002.4	MANE Select	c.631-110C>T		intron	N/A	NP_001028174.2	Q86UA6-1
	RPAIN	NM_001160244.2		c.490-110C>T		intron	N/A	NP_001153716.1	Q86UA6-2
	RPAIN	NM_001160266.2		c.426-110C>T		intron	N/A	NP_001153738.1	Q86UA6-9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RPAIN	ENST00000381209.8	TSL:1 MANE Select	c.631-110C>T		intron	N/A	ENSP00000370606.3	Q86UA6-1
	RPAIN	ENST00000381208.9	TSL:1	c.490-110C>T		intron	N/A	ENSP00000370605.5	Q86UA6-2
	RPAIN	ENST00000536255.6	TSL:1	c.314-110C>T		intron	N/A	ENSP00000439939.2	Q86UA6-6

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36231 AN: 152052 Hom.: 5693 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.214

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.330

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.222

Gnomad OTH AF: 0.243

GnomAD4 exome AF: 0.276 AC: 236920 AN: 859406 Hom.: 40967 Cov.: 11 AF XY: 0.281 AC XY: 126034 AN XY: 449236

African (AFR) AF: 0.126 AC: 2707 AN: 21488

American (AMR) AF: 0.384 AC: 15637 AN: 40680

Ashkenazi Jewish (ASJ) AF: 0.222 AC: 4691 AN: 21146

East Asian (EAS) AF: 0.796 AC: 29167 AN: 36646

South Asian (SAS) AF: 0.447 AC: 31482 AN: 70428

European-Finnish (FIN) AF: 0.309 AC: 15865 AN: 51296

Middle Eastern (MID) AF: 0.251 AC: 1020 AN: 4058

European-Non Finnish (NFE) AF: 0.219 AC: 125634 AN: 573546

Other (OTH) AF: 0.267 AC: 10717 AN: 40118

GnomAD4 genome AF: 0.238 AC: 36260 AN: 152170 Hom.: 5694 Cov.: 32 AF XY: 0.250 AC XY: 18614 AN XY: 74388

African (AFR) AF: 0.128 AC: 5316 AN: 41534

American (AMR) AF: 0.298 AC: 4550 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.214 AC: 743 AN: 3470

East Asian (EAS) AF: 0.800 AC: 4144 AN: 5182

South Asian (SAS) AF: 0.467 AC: 2258 AN: 4832

European-Finnish (FIN) AF: 0.330 AC: 3483 AN: 10558

Middle Eastern (MID) AF: 0.223 AC: 65 AN: 292

European-Non Finnish (NFE) AF: 0.222 AC: 15074 AN: 68000

Other (OTH) AF: 0.244 AC: 515 AN: 2110

Alfa AF: 0.231 Hom.: 5522

Bravo AF: 0.230

Asia WGS AF: 0.574 AC: 1993 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.3
DANN	Benign	0.46
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		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: rs8072363; hg19: chr17-5335752; COSMIC: COSV56709946; COSMIC: COSV56709946;