chr1-63370674-T-C

Variant names:

• chr1-63370674-T-C
• rs114299980
• NM_013339.4:c.-207-97T>C

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_013339.4(ALG6):​c.-207-97T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00479 in 348,170 control chromosomes in the GnomAD database, including 32 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0099 (30 hom., cov: 32)
  • Exomes 𝑓: 0.00085 (2 hom.)
• Consequence: ALG6 NM_013339.4 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.734
• Publications: 0 publications found

Genes affected

ALG6 (HGNC:23157): (ALG6 alpha-1,3-glucosyltransferase) This gene encodes a member of the ALG6/ALG8 glucosyltransferase family. The encoded protein catalyzes the addition of the first glucose residue to the growing lipid-linked oligosaccharide precursor of N-linked glycosylation. Mutations in this gene are associated with congenital disorders of glycosylation type Ic. [provided by RefSeq, Jul 2008]

ITGB3BP (HGNC:6157): (integrin subunit beta 3 binding protein) This gene encodes a transcriptional coregulator that binds to and enhances the activity of members of the nuclear receptor families, thyroid hormone receptors and retinoid X receptors. This protein also acts as a corepressor of NF-kappaB-dependent signaling. This protein induces apoptosis in breast cancer cells through a caspase 2-mediated signaling pathway. This protein is also a component of the centromere-specific histone H3 variant nucleosome associated complex (CENP-NAC) and may be involved in mitotic progression by recruiting the histone H3 variant CENP-A to the centromere. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Sep 2011]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BP6: Variant 1-63370674-T-C is Benign according to our data. Variant chr1-63370674-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 1321672.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00986 (1500/152090) while in subpopulation AFR AF = 0.0337 (1397/41480). AF 95% confidence interval is 0.0322. There are 30 homozygotes in GnomAd4. There are 708 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 30 AR,AD gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_013339.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG6	NM_013339.4	MANE Select	c.-207-97T>C		intron	N/A	NP_037471.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ALG6	ENST00000263440.6	TSL:5 MANE Select	c.-207-97T>C		intron	N/A	ENSP00000263440.5	Q9Y672
	ALG6	ENST00000948329.1		c.-207-97T>C		intron	N/A	ENSP00000618388.1
	ALG6	ENST00000920026.1		c.-207-97T>C		intron	N/A	ENSP00000590085.1

Frequencies

GnomAD3 genomes AF: 0.00985 AC: 1497 AN: 151972 Hom.: 30 Cov.: 32

Gnomad AFR AF: 0.0337

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00453

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.000323

Gnomad OTH AF: 0.00431

GnomAD4 exome AF: 0.000852 AC: 167 AN: 196080 Hom.: 2 AF XY: 0.000716 AC XY: 75 AN XY: 104768

African (AFR) AF: 0.0185 AC: 100 AN: 5398

American (AMR) AF: 0.00335 AC: 24 AN: 7170

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 5576

East Asian (EAS) AF: 0.00 AC: 0 AN: 10088

South Asian (SAS) AF: 0.0000363 AC: 1 AN: 27546

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9378

Middle Eastern (MID) AF: 0.00364 AC: 3 AN: 824

European-Non Finnish (NFE) AF: 0.000193 AC: 23 AN: 119334

Other (OTH) AF: 0.00149 AC: 16 AN: 10766

GnomAD4 genome AF: 0.00986 AC: 1500 AN: 152090 Hom.: 30 Cov.: 32 AF XY: 0.00952 AC XY: 708 AN XY: 74352

African (AFR) AF: 0.0337 AC: 1397 AN: 41480

American (AMR) AF: 0.00452 AC: 69 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5166

South Asian (SAS) AF: 0.00 AC: 0 AN: 4810

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.000324 AC: 22 AN: 68002

Other (OTH) AF: 0.00427 AC: 9 AN: 2108

Alfa AF: 0.00756 Hom.: 3

Bravo AF: 0.0111

Asia WGS AF: 0.00231 AC: 8 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.31
DANN	Benign	0.26
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114299980; hg19: chr1-63836345;