chr6-32006894-G-A

Position:

• chr6-32006894-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NR_040090.1(CYP21A1P):​n.1064G>A 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 0.0947 in 1,506,258 control chromosomes in the GnomAD database, including 19,973 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 0.10 (1866 hom., cov: 29)
  • Exomes 𝑓: 0.094 (18107 hom.)
• Consequence: CYP21A1P NR_040090.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.696

Genes affected

(HGNC:):

CYP21A1P (HGNC:2599): (cytochrome P450 family 21 subfamily A member 1, pseudogene)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CYP21A1P	NR_040090.1	n.1064G>A		non_coding_transcript_exon_variant	3/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
	ENST00000342991.10	n.1064G>A		non_coding_transcript_exon_variant	3/8	3
CYP21A1P	ENST00000354927.4	n.626G>A		non_coding_transcript_exon_variant	5/10

Frequencies

GnomAD3 genomes AF: 0.105 AC: 15117 AN: 144392 Hom.: 1871 Cov.: 29

Gnomad AFR AF: 0.141

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.0778

Gnomad ASJ AF: 0.165

Gnomad EAS AF: 0.0372

Gnomad SAS AF: 0.169

Gnomad FIN AF: 0.0603

Gnomad MID AF: 0.105

Gnomad NFE AF: 0.0915

Gnomad OTH AF: 0.121

GnomAD3 exomes AF: 0.0995 AC: 16313 AN: 163982 Hom.: 1976 AF XY: 0.103 AC XY: 8984 AN XY: 87026

Gnomad AFR exome AF: 0.153

Gnomad AMR exome AF: 0.0737

Gnomad ASJ exome AF: 0.173

Gnomad EAS exome AF: 0.0362

Gnomad SAS exome AF: 0.151

Gnomad FIN exome AF: 0.0608

Gnomad NFE exome AF: 0.0961

Gnomad OTH exome AF: 0.108

GnomAD4 exome AF: 0.0936 AC: 127503 AN: 1361756 Hom.: 18107 Cov.: 35 AF XY: 0.0950 AC XY: 63905 AN XY: 672492

Gnomad4 AFR exome AF: 0.156

Gnomad4 AMR exome AF: 0.0763

Gnomad4 ASJ exome AF: 0.171

Gnomad4 EAS exome AF: 0.0204

Gnomad4 SAS exome AF: 0.151

Gnomad4 FIN exome AF: 0.0603

Gnomad4 NFE exome AF: 0.0897

Gnomad4 OTH exome AF: 0.104

GnomAD4 genome AF: 0.105 AC: 15117 AN: 144502 Hom.: 1866 Cov.: 29 AF XY: 0.104 AC XY: 7323 AN XY: 70466

Gnomad4 AFR AF: 0.141

Gnomad4 AMR AF: 0.0777

Gnomad4 ASJ AF: 0.165

Gnomad4 EAS AF: 0.0375

Gnomad4 SAS AF: 0.168

Gnomad4 FIN AF: 0.0603

Gnomad4 NFE AF: 0.0915

Gnomad4 OTH AF: 0.119

Alfa AF: 0.0705 Hom.: 169

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.3
DANN	Benign	0.80

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

Publications

LitVar

Other links and lift over

dbSNP: rs28615950; hg19: chr6-31974671; COSMIC: COSV61590258;