rs750472

Positions:

• chr8-144476070-A-C
• chr8-144476070-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The variant allele was found at a frequency of 0.488 in 314,232 control chromosomes in the GnomAD database, including 38,518 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.50 (19244 hom., cov: 32)
  • Exomes 𝑓: 0.48 (19274 hom.)
• Consequence: Unknown
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.68

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 8-144476070-A-C is Benign according to our data. Variant chr8-144476070-A-C is described in ClinVar as [Benign]. Clinvar id is 362288.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.553 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt

Frequencies

GnomAD3 genomes AF: 0.498 AC: 75490 AN: 151722 Hom.: 19218 Cov.: 32

Gnomad AFR AF: 0.559

Gnomad AMI AF: 0.660

Gnomad AMR AF: 0.388

Gnomad ASJ AF: 0.494

Gnomad EAS AF: 0.289

Gnomad SAS AF: 0.421

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.502

Gnomad OTH AF: 0.482

GnomAD4 exome AF: 0.480 AC: 77898 AN: 162394 Hom.: 19274 Cov.: 0 AF XY: 0.481 AC XY: 39277 AN XY: 81730

Gnomad4 AFR exome AF: 0.567

Gnomad4 AMR exome AF: 0.379

Gnomad4 ASJ exome AF: 0.479

Gnomad4 EAS exome AF: 0.281

Gnomad4 SAS exome AF: 0.456

Gnomad4 FIN exome AF: 0.511

Gnomad4 NFE exome AF: 0.503

Gnomad4 OTH exome AF: 0.486

GnomAD4 genome AF: 0.498 AC: 75565 AN: 151838 Hom.: 19244 Cov.: 32 AF XY: 0.493 AC XY: 36552 AN XY: 74194

Gnomad4 AFR AF: 0.559

Gnomad4 AMR AF: 0.388

Gnomad4 ASJ AF: 0.494

Gnomad4 EAS AF: 0.289

Gnomad4 SAS AF: 0.422

Gnomad4 FIN AF: 0.510

Gnomad4 NFE AF: 0.502

Gnomad4 OTH AF: 0.484

Alfa AF: 0.494 Hom.: 17832

Bravo AF: 0.489

Asia WGS AF: 0.405 AC: 1409 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Holoprosencephaly sequence Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 12, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 11, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.23
DANN	Benign	0.40

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: rs750472; hg19: chr8-145701453; COSMIC: COSV56763057; COSMIC: COSV56763057;