rs61199332

Positions:

• chr8-11573132-C-T

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 0.0602 in 152,304 control chromosomes in the GnomAD database, including 563 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Genomes: 𝑓 0.060 (563 hom., cov: 33)
• Consequence: Unknown
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts P:1 B:3
• Conservation: PhyloP100: -0.0330

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 8-11573132-C-T is Benign according to our data. Variant chr8-11573132-C-T is described in ClinVar as [Benign]. Clinvar id is 12321.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.155 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: 0.0600 AC: 9134 AN: 152186 Hom.: 555 Cov.: 33

Gnomad AFR AF: 0.158

Gnomad AMI AF: 0.00658

Gnomad AMR AF: 0.0306

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.00711

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.00847

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0224

Gnomad OTH AF: 0.0550

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0602 AC: 9168 AN: 152304 Hom.: 563 Cov.: 33 AF XY: 0.0591 AC XY: 4402 AN XY: 74478

Gnomad4 AFR AF: 0.159

Gnomad4 AMR AF: 0.0304

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.00713

Gnomad4 SAS AF: 0.0396

Gnomad4 FIN AF: 0.00847

Gnomad4 NFE AF: 0.0224

Gnomad4 OTH AF: 0.0545

Alfa AF: 0.0472 Hom.: 98

Bravo AF: 0.0662

Asia WGS AF: 0.0390 AC: 134 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity-onset diabetes of the young type 11 Pathogenic:1 Benign:1

Benign, no assertion criteria provided	curation	Reproductive Health Research and Development, BGI Genomics	Jan 06, 2020	NC_000008.11:g.11573132C>T has an allele frequency of 0.163 in African subpopulation in the gnomAD database, including 128 homozygous occurrences. This variant was annotated at the position 11,468,050 on chromsome 8. In the functional study by MIN6 beta-cells, this variant decreased luciferase expression as compared with control constructs without any insert (PMID: 19667185). This evidence suggests the variant to be classified as benign. ACMG/AMP criteria applied: BA1, BS2, PS3. -
Pathogenic, no assertion criteria provided	literature only	OMIM	Aug 25, 2009	- -

not specified Benign:1

Benign, criteria provided, single submitter

research

H3Africa Consortium

Oct 28, 2020

While the frequency of the alternate allele in gnoMAD v2.0.2 is 0.146, its frequency in African populations is >5%. This suggests that previous classifications of this variant as pathogenic are in error. -

BLK-related disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 12, 2020

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	3.4
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs61199332; hg19: chr8-11430641;