8-142875735-A-T

Variant names:

• chr8-142875735-A-T
• rs61752769
• NM_000497.4:c.1098T>A

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_000497.4(CYP11B1):​c.1098T>A​(p.Arg366Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,140 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. R366R) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: CYP11B1 NM_000497.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00200
• Publications: 4 publications found

Genes affected

CYP11B1 (HGNC:2591): (cytochrome P450 family 11 subfamily B member 1) This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the mitochondrial inner membrane and is involved in the conversion of progesterone to cortisol in the adrenal cortex. Mutations in this gene cause congenital adrenal hyperplasia due to 11-beta-hydroxylase deficiency. Transcript variants encoding different isoforms have been noted for this gene. [provided by RefSeq, Jul 2008]

GML (HGNC:4375): (glycosylphosphatidylinositol anchored molecule like) Predicted to be involved in DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest; apoptotic process; and negative regulation of cell population proliferation. Predicted to be extrinsic component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.65).
• BP7: Synonymous conserved (PhyloP=-0.002 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000497.4. 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
	CYP11B1	NM_000497.4	MANE Select	c.1098T>A	p.Arg366Arg	synonymous	Exon 6 of 9	NP_000488.3
	CYP11B1	NM_001026213.1		c.1098T>A	p.Arg366Arg	synonymous	Exon 6 of 8	NP_001021384.1	P15538-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CYP11B1	ENST00000292427.10	TSL:1 MANE Select	c.1098T>A	p.Arg366Arg	synonymous	Exon 6 of 9	ENSP00000292427.5	P15538-1
	CYP11B1	ENST00000377675.3	TSL:1	c.1311T>A	p.Arg437Arg	synonymous	Exon 8 of 11	ENSP00000366903.3	Q4VAR0
	CYP11B1	ENST00000517471.5	TSL:1	c.1098T>A	p.Arg366Arg	synonymous	Exon 6 of 8	ENSP00000428043.1	P15538-2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD2 exomes AF: 0.00000400 AC: 1 AN: 249754 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000463

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461140 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 726914

African (AFR) AF: 0.00 AC: 0 AN: 33404

American (AMR) AF: 0.00 AC: 0 AN: 44694

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26102

East Asian (EAS) AF: 0.00 AC: 0 AN: 39598

South Asian (SAS) AF: 0.00 AC: 0 AN: 86242

European-Finnish (FIN) AF: 0.0000187 AC: 1 AN: 53338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5758

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111666

Other (OTH) AF: 0.00 AC: 0 AN: 60338

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.9
DANN	Benign	0.72
PhyloP100		-0.0020
PromoterAI		-0.012	Neutral

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: rs61752769; hg19: chr8-143957151;