rs2243621

Variant names:

• chr6-31464043-C-T
• rs2243621
• ENST00000541196.3:n.198-10C>T

Variant summary

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

The ENST00000414046.3(HCP5):​n.783C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 434,120 control chromosomes in the GnomAD database, including 9,709 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 0.21 (4010 hom., cov: 32)
  • Exomes 𝑓: 0.18 (5699 hom.)
• Consequence: HCP5 ENST00000414046.3 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.179
• Publications: 22 publications found

Genes affected

HCP5 (HGNC:21659): (HLA complex P5)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000414046.3. 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
	HCP5	NR_040662.1		n.773C>T		non_coding_transcript_exon	Exon 2 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	HCP5	ENST00000541196.3	TSL:1	n.198-10C>T		intron	N/A
	HCP5	ENST00000414046.3	TSL:4	n.783C>T		non_coding_transcript_exon	Exon 2 of 2
	HCP5	ENST00000670109.1		n.746C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes AF: 0.210 AC: 31892 AN: 151568 Hom.: 4001 Cov.: 32

Gnomad AFR AF: 0.286

Gnomad AMI AF: 0.189

Gnomad AMR AF: 0.252

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.0655

Gnomad SAS AF: 0.0957

Gnomad FIN AF: 0.321

Gnomad MID AF: 0.232

Gnomad NFE AF: 0.163

Gnomad OTH AF: 0.206

GnomAD2 exomes AF: 0.194 AC: 34517 AN: 177968 AF XY: 0.187

Gnomad AFR exome AF: 0.298

Gnomad AMR exome AF: 0.276

Gnomad ASJ exome AF: 0.105

Gnomad EAS exome AF: 0.0581

Gnomad FIN exome AF: 0.317

Gnomad NFE exome AF: 0.174

Gnomad OTH exome AF: 0.175

GnomAD4 exome AF: 0.181 AC: 51037 AN: 282434 Hom.: 5699 Cov.: 0 AF XY: 0.171 AC XY: 27490 AN XY: 160624

African (AFR) AF: 0.295 AC: 1971 AN: 6688

American (AMR) AF: 0.273 AC: 5897 AN: 21622

Ashkenazi Jewish (ASJ) AF: 0.101 AC: 720 AN: 7124

East Asian (EAS) AF: 0.0721 AC: 617 AN: 8560

South Asian (SAS) AF: 0.110 AC: 5700 AN: 51818

European-Finnish (FIN) AF: 0.303 AC: 9140 AN: 30192

Middle Eastern (MID) AF: 0.243 AC: 617 AN: 2534

European-Non Finnish (NFE) AF: 0.172 AC: 24286 AN: 141548

Other (OTH) AF: 0.169 AC: 2089 AN: 12348

GnomAD4 genome AF: 0.211 AC: 31955 AN: 151686 Hom.: 4010 Cov.: 32 AF XY: 0.216 AC XY: 15984 AN XY: 74144

African (AFR) AF: 0.287 AC: 11836 AN: 41238

American (AMR) AF: 0.252 AC: 3835 AN: 15200

Ashkenazi Jewish (ASJ) AF: 0.0900 AC: 311 AN: 3456

East Asian (EAS) AF: 0.0659 AC: 338 AN: 5130

South Asian (SAS) AF: 0.0960 AC: 462 AN: 4814

European-Finnish (FIN) AF: 0.321 AC: 3393 AN: 10584

Middle Eastern (MID) AF: 0.226 AC: 66 AN: 292

European-Non Finnish (NFE) AF: 0.164 AC: 11112 AN: 67952

Other (OTH) AF: 0.204 AC: 430 AN: 2108

Alfa AF: 0.198 Hom.: 3591

Bravo AF: 0.208

Asia WGS AF: 0.108 AC: 374 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	5.6
DANN	Benign	0.36
PhyloP100		0.18

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs2243621;

hg19: chr6-31431820;

COSMIC: COSV69993674;