chr11-62634148-C-T

Variant names:

• chr11-62634148-C-T
• rs11231168
• NM_198334.3:c.561-634G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_198334.3(GANAB):​c.561-634G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.336 in 151,988 control chromosomes in the GnomAD database, including 10,832 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.34 (10832 hom., cov: 31)
• Consequence: GANAB NM_198334.3 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.767
• Publications: 20 publications found

Genes affected

GANAB (HGNC:4138): (glucosidase II alpha subunit) This gene encodes the alpha subunit of glucosidase II and a member of the glycosyl hydrolase 31 family of proteins. The heterodimeric enzyme glucosidase II plays a role in protein folding and quality control by cleaving glucose residues from immature glycoproteins in the endoplasmic reticulum. Expression of the encoded protein is elevated in lung tumor tissue and in response to UV irradiation. Mutations in this gene cause autosomal-dominant polycystic kidney and liver disease. [provided by RefSeq, Jul 2016]

GANAB Gene-Disease associations (from GenCC):

• polycystic kidney disease 3 with or without polycystic liver disease

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: ClinGen, Genomics England PanelApp, Labcorp Genetics (formerly Invitae)
• autosomal dominant polycystic kidney disease

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BP6: Variant 11-62634148-C-T is Benign according to our data. Variant chr11-62634148-C-T is described in ClinVar as [Benign]. Clinvar id is 1253642.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.517 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GANAB	NM_198334.3	c.561-634G>A		intron_variant	Intron 5 of 23	ENST00000356638.8	NP_938148.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GANAB	ENST00000356638.8	c.561-634G>A		intron_variant	Intron 5 of 23	1	NM_198334.3	ENSP00000349053.3

Frequencies

GnomAD3 genomes AF: 0.336 AC: 51007 AN: 151870 Hom.: 10820 Cov.: 31

Gnomad AFR AF: 0.0797

Gnomad AMI AF: 0.429

Gnomad AMR AF: 0.479

Gnomad ASJ AF: 0.332

Gnomad EAS AF: 0.242

Gnomad SAS AF: 0.533

Gnomad FIN AF: 0.584

Gnomad MID AF: 0.320

Gnomad NFE AF: 0.413

Gnomad OTH AF: 0.342

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

GnomAD4 genome AF: 0.336 AC: 51029 AN: 151988 Hom.: 10832 Cov.: 31 AF XY: 0.347 AC XY: 25800 AN XY: 74268

African (AFR) AF: 0.0796 AC: 3303 AN: 41510

American (AMR) AF: 0.479 AC: 7303 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.332 AC: 1153 AN: 3470

East Asian (EAS) AF: 0.242 AC: 1248 AN: 5166

South Asian (SAS) AF: 0.534 AC: 2572 AN: 4812

European-Finnish (FIN) AF: 0.584 AC: 6161 AN: 10554

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.413 AC: 28080 AN: 67928

Other (OTH) AF: 0.343 AC: 722 AN: 2106

Alfa AF: 0.381 Hom.: 23444

Bravo AF: 0.315

Asia WGS AF: 0.411 AC: 1428 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 21, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	6.1
DANN	Benign	0.77
PhyloP100		0.77
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs11231168; hg19: chr11-62401620; COSMIC: COSV60464436; COSMIC: COSV60464436;