rs28691121

Positions:

• chr6-32006941-G-A

Variant summary

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

The ENST00000342991.10(ENSG00000290788):​n.1081+30G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0663 in 1,501,740 control chromosomes in the GnomAD database, including 7,988 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 0.099 (1188 hom., cov: 29)
  • Exomes 𝑓: 0.063 (6800 hom.)
• Consequence: ENSG00000290788 ENST00000342991.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.62

Genes affected

ENSG00000290788 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.181 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP21A1P	NR_040090.1	n.1081+30G>A		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
ENSG00000290788	ENST00000342991.10	n.1081+30G>A		intron_variant		3
CYP21A1P	ENST00000354927.4	n.643+30G>A		intron_variant		6

Frequencies

GnomAD3 genomes AF: 0.0989 AC: 14185 AN: 143426 Hom.: 1183 Cov.: 29

Gnomad AFR AF: 0.185

Gnomad AMI AF: 0.156

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0272

Gnomad EAS AF: 0.0297

Gnomad SAS AF: 0.0564

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0855

Gnomad NFE AF: 0.0609

Gnomad OTH AF: 0.0930

GnomAD3 exomes AF: 0.0653 AC: 10527 AN: 161144 Hom.: 875 AF XY: 0.0637 AC XY: 5458 AN XY: 85702

Gnomad AFR exome AF: 0.199

Gnomad AMR exome AF: 0.0410

Gnomad ASJ exome AF: 0.0326

Gnomad EAS exome AF: 0.0226

Gnomad SAS exome AF: 0.0554

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0582

Gnomad OTH exome AF: 0.0619

GnomAD4 exome AF: 0.0628 AC: 85308 AN: 1358200 Hom.: 6800 Cov.: 35 AF XY: 0.0623 AC XY: 41814 AN XY: 670754

Gnomad4 AFR exome AF: 0.185

Gnomad4 AMR exome AF: 0.0475

Gnomad4 ASJ exome AF: 0.0341

Gnomad4 EAS exome AF: 0.0507

Gnomad4 SAS exome AF: 0.0550

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0581

Gnomad4 OTH exome AF: 0.0692

GnomAD4 genome AF: 0.0991 AC: 14224 AN: 143540 Hom.: 1188 Cov.: 29 AF XY: 0.0999 AC XY: 6991 AN XY: 69960

Gnomad4 AFR AF: 0.185

Gnomad4 AMR AF: 0.0650

Gnomad4 ASJ AF: 0.0272

Gnomad4 EAS AF: 0.0297

Gnomad4 SAS AF: 0.0574

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0610

Gnomad4 OTH AF: 0.0980

Alfa AF: 0.0697 Hom.: 165

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.59

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

Publications

LitVar

Other links and lift over

dbSNP: rs28691121; hg19: chr6-31974718; COSMIC: COSV61590007;