rs41315836

Variant names:

• chr6-32007374-T-G
• rs41315836
• ENST00000342991.10:n.1274T>G

Variant summary

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

The ENST00000342991.10(ENSG00000290788):​n.1274T>G 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 0.218 in 1,341,104 control chromosomes in the GnomAD database, including 90,030 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 0.32 (11437 hom., cov: 26)
  • Exomes 𝑓: 0.21 (78593 hom.)
• Consequence: ENSG00000290788 ENST00000342991.10 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.03
• Publications: 5 publications found

Genes affected

ENSG00000290788 (HGNC:):

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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.54 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000342991.10. 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
	CYP21A1P	NR_040090.1		n.1274T>G		non_coding_transcript_exon	Exon 5 of 8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000290788	ENST00000342991.10	TSL:3	n.1274T>G		non_coding_transcript_exon	Exon 5 of 8
	CYP21A1P	ENST00000354927.4	TSL:6	n.836T>G		non_coding_transcript_exon	Exon 7 of 10

Frequencies

GnomAD3 genomes AF: 0.324 AC: 44500 AN: 137376 Hom.: 11424 Cov.: 26

Gnomad AFR AF: 0.546

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.284

Gnomad ASJ AF: 0.265

Gnomad EAS AF: 0.204

Gnomad SAS AF: 0.420

Gnomad FIN AF: 0.134

Gnomad MID AF: 0.340

Gnomad NFE AF: 0.240

Gnomad OTH AF: 0.359

GnomAD2 exomes AF: 0.253 AC: 56949 AN: 225024 AF XY: 0.261

Gnomad AFR exome AF: 0.565

Gnomad AMR exome AF: 0.180

Gnomad ASJ exome AF: 0.201

Gnomad EAS exome AF: 0.195

Gnomad FIN exome AF: 0.133

Gnomad NFE exome AF: 0.223

Gnomad OTH exome AF: 0.253

GnomAD4 exome AF: 0.206 AC: 248476 AN: 1203630 Hom.: 78593 Cov.: 38 AF XY: 0.213 AC XY: 127899 AN XY: 601202

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.572 AC: 15129 AN: 26466

American (AMR) AF: 0.173 AC: 6694 AN: 38752

Ashkenazi Jewish (ASJ) AF: 0.208 AC: 4630 AN: 22282

East Asian (EAS) AF: 0.214 AC: 7764 AN: 36362

South Asian (SAS) AF: 0.421 AC: 31662 AN: 75164

European-Finnish (FIN) AF: 0.134 AC: 6583 AN: 49164

Middle Eastern (MID) AF: 0.217 AC: 1041 AN: 4790

European-Non Finnish (NFE) AF: 0.181 AC: 162682 AN: 899838

Other (OTH) AF: 0.242 AC: 12291 AN: 50812

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.324 AC: 44544 AN: 137474 Hom.: 11437 Cov.: 26 AF XY: 0.320 AC XY: 21427 AN XY: 67016

African (AFR) AF: 0.546 AC: 19674 AN: 36002

American (AMR) AF: 0.284 AC: 3970 AN: 14002

Ashkenazi Jewish (ASJ) AF: 0.265 AC: 849 AN: 3200

East Asian (EAS) AF: 0.204 AC: 978 AN: 4784

South Asian (SAS) AF: 0.418 AC: 1783 AN: 4262

European-Finnish (FIN) AF: 0.134 AC: 1299 AN: 9686

Middle Eastern (MID) AF: 0.332 AC: 91 AN: 274

European-Non Finnish (NFE) AF: 0.240 AC: 15039 AN: 62586

Other (OTH) AF: 0.355 AC: 661 AN: 1864

Alfa AF: 0.283 Hom.: 1748

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	18
DANN	Benign	0.90
PhyloP100		1.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0

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: rs41315836;

hg19: chr6-31975151;

COSMIC: COSV61589954;