6-31623121-C-T

Variant names:

• chr6-31623121-C-T
• rs2736172
• NM_004638.4:c.112+220C>T

Variant summary

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

The NM_004638.4(PRRC2A):​c.112+220C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.384 in 758,090 control chromosomes in the GnomAD database, including 61,698 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 (8633 hom., cov: 32)
  • Exomes 𝑓: 0.40 (53065 hom.)
• Consequence: PRRC2A NM_004638.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 42 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]

SNORA38 (HGNC:32631): (small nucleolar RNA, H/ACA box 38)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.573 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.112+220C>T		intron	N/A	NP_004629.3
	PRRC2A	NM_080686.3		c.112+220C>T		intron	N/A	NP_542417.2	A0A1U9X974
	SNORA38	NR_002971.1		n.43C>T		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PRRC2A	ENST00000376033.3	TSL:1 MANE Select	c.112+220C>T		intron	N/A	ENSP00000365201.2	P48634-1
	PRRC2A	ENST00000376007.8	TSL:1	c.112+220C>T		intron	N/A	ENSP00000365175.4	P48634-1
	SNORA38	ENST00000363946.1	TSL:6	n.43C>T		non_coding_transcript_exon	Exon 1 of 1

Frequencies

GnomAD3 genomes AF: 0.301 AC: 45634 AN: 151836 Hom.: 8625 Cov.: 32

Gnomad AFR AF: 0.0798

Gnomad AMI AF: 0.518

Gnomad AMR AF: 0.348

Gnomad ASJ AF: 0.547

Gnomad EAS AF: 0.590

Gnomad SAS AF: 0.529

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.421

Gnomad NFE AF: 0.366

Gnomad OTH AF: 0.330

GnomAD2 exomes AF: 0.408 AC: 95559 AN: 233992 AF XY: 0.419

Gnomad AFR exome AF: 0.0713

Gnomad AMR exome AF: 0.414

Gnomad ASJ exome AF: 0.560

Gnomad EAS exome AF: 0.582

Gnomad FIN exome AF: 0.322

Gnomad NFE exome AF: 0.385

Gnomad OTH exome AF: 0.399

GnomAD4 exome AF: 0.405 AC: 245316 AN: 606136 Hom.: 53065 Cov.: 3 AF XY: 0.417 AC XY: 138179 AN XY: 331616

African (AFR) AF: 0.0824 AC: 1444 AN: 17526

American (AMR) AF: 0.409 AC: 17792 AN: 43458

Ashkenazi Jewish (ASJ) AF: 0.551 AC: 11495 AN: 20848

East Asian (EAS) AF: 0.570 AC: 20265 AN: 35546

South Asian (SAS) AF: 0.524 AC: 36070 AN: 68840

European-Finnish (FIN) AF: 0.317 AC: 11767 AN: 37092

Middle Eastern (MID) AF: 0.451 AC: 1859 AN: 4126

European-Non Finnish (NFE) AF: 0.382 AC: 132092 AN: 346064

Other (OTH) AF: 0.384 AC: 12532 AN: 32636

GnomAD4 genome AF: 0.300 AC: 45653 AN: 151954 Hom.: 8633 Cov.: 32 AF XY: 0.306 AC XY: 22695 AN XY: 74230

African (AFR) AF: 0.0798 AC: 3309 AN: 41456

American (AMR) AF: 0.348 AC: 5317 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.547 AC: 1897 AN: 3468

East Asian (EAS) AF: 0.590 AC: 3055 AN: 5176

South Asian (SAS) AF: 0.529 AC: 2549 AN: 4822

European-Finnish (FIN) AF: 0.317 AC: 3333 AN: 10508

Middle Eastern (MID) AF: 0.425 AC: 125 AN: 294

European-Non Finnish (NFE) AF: 0.366 AC: 24892 AN: 67958

Other (OTH) AF: 0.336 AC: 706 AN: 2104

Alfa AF: 0.352 Hom.: 11611

Bravo AF: 0.290

Asia WGS AF: 0.540 AC: 1877 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.81
PhyloP100		-0.17
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: rs2736172; hg19: chr6-31590898;