6-31634066-T-C

Variant names:

• chr6-31634066-T-C
• rs3115663
• NM_004638.4:c.4719+77T>C

Variant summary

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

The NM_004638.4(PRRC2A):​c.4719+77T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.176 in 1,579,806 control chromosomes in the GnomAD database, including 26,347 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 0.17 (2374 hom., cov: 32)
  • Exomes 𝑓: 0.18 (23973 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.20
• Publications: 52 publications found

Genes affected

PRRC2A (HGNC:13918): (proline rich coiled-coil 2A) A cluster of genes, BAT1-BAT5, has been localized in the vicinity of the genes for TNF alpha and TNF beta. These genes are all within the human major histocompatibility complex class III region. This gene has microsatellite repeats which are associated with the age-at-onset of insulin-dependent diabetes mellitus (IDDM) and possibly thought to be involved with the inflammatory process of pancreatic beta-cell destruction during the development of IDDM. This gene is also a candidate gene for the development of rheumatoid arthritis. Two transcript variants encoding the same protein have been found for this gene. [provided by RefSeq, Dec 2010]

MIR6832 (HGNC:50140): (microRNA 6832) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004638.4. 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
	PRRC2A	NM_004638.4	MANE Select	c.4719+77T>C		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.4719+77T>C		intron	N/A	NP_542417.2	A0A1U9X974
	MIR6832	NR_106890.1		n.*208T>C		downstream_gene	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.4719+77T>C		intron	N/A	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.4719+77T>C		intron	N/A	ENSP00000365175.4	P48634-1
	PRRC2A	ENST00000460302.1	TSL:3	n.113T>C		non_coding_transcript_exon	Exon 1 of 2

Frequencies

GnomAD3 genomes AF: 0.169 AC: 25671 AN: 152064 Hom.: 2374 Cov.: 32

Gnomad AFR AF: 0.193

Gnomad AMI AF: 0.173

Gnomad AMR AF: 0.0987

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0786

Gnomad SAS AF: 0.124

Gnomad FIN AF: 0.161

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.149

GnomAD4 exome AF: 0.177 AC: 253153 AN: 1427624 Hom.: 23973 Cov.: 34 AF XY: 0.175 AC XY: 124191 AN XY: 710462

African (AFR) AF: 0.208 AC: 6462 AN: 31072

American (AMR) AF: 0.0835 AC: 2772 AN: 33188

Ashkenazi Jewish (ASJ) AF: 0.119 AC: 2930 AN: 24596

East Asian (EAS) AF: 0.0463 AC: 1834 AN: 39576

South Asian (SAS) AF: 0.116 AC: 9307 AN: 80436

European-Finnish (FIN) AF: 0.160 AC: 8357 AN: 52074

Middle Eastern (MID) AF: 0.0908 AC: 514 AN: 5660

European-Non Finnish (NFE) AF: 0.192 AC: 211214 AN: 1102020

Other (OTH) AF: 0.165 AC: 9763 AN: 59002

GnomAD4 genome AF: 0.169 AC: 25671 AN: 152182 Hom.: 2374 Cov.: 32 AF XY: 0.164 AC XY: 12223 AN XY: 74412

African (AFR) AF: 0.193 AC: 8010 AN: 41504

American (AMR) AF: 0.0984 AC: 1505 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.115 AC: 399 AN: 3468

East Asian (EAS) AF: 0.0792 AC: 410 AN: 5180

South Asian (SAS) AF: 0.124 AC: 600 AN: 4828

European-Finnish (FIN) AF: 0.161 AC: 1711 AN: 10606

Middle Eastern (MID) AF: 0.170 AC: 50 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12518 AN: 67986

Other (OTH) AF: 0.147 AC: 311 AN: 2112

Alfa AF: 0.177 Hom.: 5871

Bravo AF: 0.166

Asia WGS AF: 0.0960 AC: 332 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.14
DANN	Benign	0.51
PhyloP100		-1.2
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
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: rs3115663; hg19: chr6-31601843;