11-78139778-C-G

Variant names:

• chr11-78139778-C-G
• rs2156785
• ENST00000532831.2:n.8C>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The ENST00000532831.2(KCTD21-AS1):​n.8C>G variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00156 in 637,204 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0046 (4 hom., cov: 34)
  • Exomes 𝑓: 0.00060 (3 hom.)
• Consequence: KCTD21-AS1 ENST00000532831.2 non_coding_transcript_exon
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.02

Genes affected

KCTD21-AS1 (HGNC:48674): (KCTD21 antisense RNA 1)

ALG8 (HGNC:23161): (ALG8 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the second glucose residue to the lipid-linked oligosaccharide precursor for N-linked glycosylation of proteins. Mutations in this gene have been associated with congenital disorder of glycosylation type Ih (CDG-Ih). Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 11-78139778-C-G is Benign according to our data. Variant chr11-78139778-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 1203400.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00461 (702/152272) while in subpopulation AFR AF= 0.0162 (674/41566). AF 95% confidence interval is 0.0152. There are 4 homozygotes in gnomad4. There are 324 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ALG8	NM_024079.5	c.-190G>C		upstream_gene_variant		ENST00000299626.10	NP_076984.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ALG8	ENST00000299626.10	c.-190G>C		upstream_gene_variant		1	NM_024079.5	ENSP00000299626.5

Frequencies

GnomAD3 genomes AF: 0.00459 AC: 699 AN: 152154 Hom.: 3 Cov.: 34

Gnomad AFR AF: 0.0162

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000654

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000604 AC: 293 AN: 484932 Hom.: 3 Cov.: 5 AF XY: 0.000486 AC XY: 125 AN XY: 257022

Gnomad4 AFR exome AF: 0.0166

Gnomad4 AMR exome AF: 0.000668

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000201

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000650

Gnomad4 OTH exome AF: 0.00128

GnomAD4 genome AF: 0.00461 AC: 702 AN: 152272 Hom.: 4 Cov.: 34 AF XY: 0.00435 AC XY: 324 AN XY: 74448

Gnomad4 AFR AF: 0.0162

Gnomad4 AMR AF: 0.000653

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.00426

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 10, 2018

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.15
DANN	Benign	0.48

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs2156785; hg19: chr11-77850824;