chr8-58491017-C-T

Position:

• chr8-58491017-C-T

Variant summary

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

The NM_000780.4(CYP7A1):​c.*458G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 156,314 control chromosomes in the GnomAD database, including 9,965 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 0.35 (9649 hom., cov: 32)
  • Exomes 𝑓: 0.36 (316 hom.)
• Consequence: CYP7A1 NM_000780.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.203

Genes affected

CYP7A1 (HGNC:2651): (cytochrome P450 family 7 subfamily A 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 endoplasmic reticulum membrane protein catalyzes the first reaction in the cholesterol catabolic pathway in the liver, which converts cholesterol to bile acids. This reaction is the rate limiting step and the major site of regulation of bile acid synthesis, which is the primary mechanism for the removal of cholesterol from the body. Polymorphisms in the promoter of this gene are associated with defects in bile acid synthesis. [provided by RefSeq, Feb 2010]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CYP7A1	NM_000780.4	c.*458G>A		3_prime_UTR_variant	6/6	ENST00000301645.4	NP_000771.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CYP7A1	ENST00000301645	c.*458G>A		3_prime_UTR_variant	6/6	1	NM_000780.4	ENSP00000301645.3

Frequencies

GnomAD3 genomes AF: 0.347 AC: 52689 AN: 151900 Hom.: 9642 Cov.: 32

Gnomad AFR AF: 0.234

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.362

Gnomad EAS AF: 0.307

Gnomad SAS AF: 0.396

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.355

GnomAD4 exome AF: 0.365 AC: 1568 AN: 4296 Hom.: 316 Cov.: 0 AF XY: 0.368 AC XY: 806 AN XY: 2190

Gnomad4 AFR exome AF: 0.212

Gnomad4 AMR exome AF: 0.487

Gnomad4 ASJ exome AF: 0.295

Gnomad4 EAS exome AF: 0.341

Gnomad4 SAS exome AF: 0.342

Gnomad4 FIN exome AF: 0.362

Gnomad4 NFE exome AF: 0.366

Gnomad4 OTH exome AF: 0.372

GnomAD4 genome AF: 0.347 AC: 52726 AN: 152018 Hom.: 9649 Cov.: 32 AF XY: 0.349 AC XY: 25897 AN XY: 74302

Gnomad4 AFR AF: 0.234

Gnomad4 AMR AF: 0.464

Gnomad4 ASJ AF: 0.362

Gnomad4 EAS AF: 0.307

Gnomad4 SAS AF: 0.395

Gnomad4 FIN AF: 0.374

Gnomad4 NFE AF: 0.383

Gnomad4 OTH AF: 0.357

Alfa AF: 0.376 Hom.: 22901

Bravo AF: 0.348

Asia WGS AF: 0.372 AC: 1292 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.92
DANN	Benign	0.42

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: rs8192879; hg19: chr8-59403576;