chr11-78114229-A-G

Variant names:

• chr11-78114229-A-G
• rs10899440
• NM_024079.5:c.673+37T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_024079.5(ALG8):​c.673+37T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.434 in 1,611,950 control chromosomes in the GnomAD database, including 155,368 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.37 (11725 hom., cov: 32)
  • Exomes 𝑓: 0.44 (143643 hom.)
• Consequence: ALG8 NM_024079.5 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.872
• Publications: 20 publications found

Genes affected

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]

ALG8 Gene-Disease associations (from GenCC):

• ALG8-congenital disorder of glycosylation

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: PanelApp Australia, G2P, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• polycystic liver disease 3 with or without kidney cysts

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 11-78114229-A-G is Benign according to our data. Variant chr11-78114229-A-G is described in ClinVar as Benign. ClinVar VariationId is 261681.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.451 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024079.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	NM_024079.5	MANE Select	c.673+37T>C		intron	N/A	NP_076984.2
	ALG8	NM_001425224.1		c.766+37T>C		intron	N/A	NP_001412153.1
	ALG8	NM_001425225.1		c.673+37T>C		intron	N/A	NP_001412154.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG8	ENST00000299626.10	TSL:1 MANE Select	c.673+37T>C		intron	N/A	ENSP00000299626.5
	ALG8	ENST00000532050.5	TSL:1	n.*57+37T>C		intron	N/A	ENSP00000437199.1
	ALG8	ENST00000679559.1		c.673+37T>C		intron	N/A	ENSP00000505433.1

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56947 AN: 151932 Hom.: 11711 Cov.: 32

Gnomad AFR AF: 0.196

Gnomad AMI AF: 0.370

Gnomad AMR AF: 0.366

Gnomad ASJ AF: 0.408

Gnomad EAS AF: 0.361

Gnomad SAS AF: 0.417

Gnomad FIN AF: 0.548

Gnomad MID AF: 0.339

Gnomad NFE AF: 0.455

Gnomad OTH AF: 0.386

GnomAD2 exomes AF: 0.420 AC: 104332 AN: 248584 AF XY: 0.426

Gnomad AFR exome AF: 0.185

Gnomad AMR exome AF: 0.368

Gnomad ASJ exome AF: 0.404

Gnomad EAS exome AF: 0.359

Gnomad FIN exome AF: 0.547

Gnomad NFE exome AF: 0.459

Gnomad OTH exome AF: 0.438

GnomAD4 exome AF: 0.440 AC: 642072 AN: 1459900 Hom.: 143643 Cov.: 40 AF XY: 0.440 AC XY: 319842 AN XY: 726312

African (AFR) AF: 0.182 AC: 6097 AN: 33464

American (AMR) AF: 0.370 AC: 16511 AN: 44622

Ashkenazi Jewish (ASJ) AF: 0.406 AC: 10605 AN: 26122

East Asian (EAS) AF: 0.312 AC: 12387 AN: 39666

South Asian (SAS) AF: 0.407 AC: 35104 AN: 86152

European-Finnish (FIN) AF: 0.538 AC: 28452 AN: 52856

Middle Eastern (MID) AF: 0.377 AC: 2171 AN: 5760

European-Non Finnish (NFE) AF: 0.455 AC: 505267 AN: 1110920

Other (OTH) AF: 0.422 AC: 25478 AN: 60338

GnomAD4 genome AF: 0.375 AC: 56979 AN: 152050 Hom.: 11725 Cov.: 32 AF XY: 0.379 AC XY: 28160 AN XY: 74320

African (AFR) AF: 0.196 AC: 8115 AN: 41484

American (AMR) AF: 0.366 AC: 5590 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.408 AC: 1415 AN: 3468

East Asian (EAS) AF: 0.361 AC: 1867 AN: 5174

South Asian (SAS) AF: 0.417 AC: 2010 AN: 4824

European-Finnish (FIN) AF: 0.548 AC: 5771 AN: 10532

Middle Eastern (MID) AF: 0.347 AC: 102 AN: 294

European-Non Finnish (NFE) AF: 0.455 AC: 30943 AN: 67978

Other (OTH) AF: 0.393 AC: 829 AN: 2110

Alfa AF: 0.379 Hom.: 9998

Bravo AF: 0.354

Asia WGS AF: 0.414 AC: 1444 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Jul 05, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

not specified Benign:1

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	7.4
DANN	Benign	0.57
PhyloP100		0.87
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs10899440; hg19: chr11-77825275; COSMIC: COSV55200303; COSMIC: COSV55200303;