NM_020156.5:c.221-623G>T

Variant names:

• chr7-7237632-G-T
• rs10487590
• NM_020156.5:c.221-623G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_020156.5(C1GALT1):​c.221-623G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.146 in 152,146 control chromosomes in the GnomAD database, including 2,022 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.15 (2022 hom., cov: 32)
• Consequence: C1GALT1 NM_020156.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.156
• Publications: 4 publications found

Genes affected

C1GALT1 (HGNC:24337): (core 1 synthase, glycoprotein-N-acetylgalactosamine 3-beta-galactosyltransferase 1) The protein encoded by this gene generates the common core 1 O-glycan structure, Gal-beta-1-3GalNAc-R, by the transfer of Gal from UDP-Gal to GalNAc-alpha-1-R. Core 1 is a precursor for many extended mucin-type O-glycans on cell surface and secreted glycoproteins. Studies in mice suggest that this gene plays a key role in thrombopoiesis and kidney homeostasis.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.2 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020156.5. 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
	C1GALT1	NM_020156.5	MANE Select	c.221-623G>T		intron	N/A	NP_064541.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	C1GALT1	ENST00000436587.7	TSL:5 MANE Select	c.221-623G>T		intron	N/A	ENSP00000389176.2
	C1GALT1	ENST00000223122.4	TSL:1	c.221-623G>T		intron	N/A	ENSP00000223122.2
	C1GALT1	ENST00000402468.3	TSL:1	c.221-623G>T		intron	N/A	ENSP00000384550.3

Frequencies

GnomAD3 genomes AF: 0.146 AC: 22207 AN: 152028 Hom.: 2023 Cov.: 32

Gnomad AFR AF: 0.0712

Gnomad AMI AF: 0.162

Gnomad AMR AF: 0.173

Gnomad ASJ AF: 0.296

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0652

Gnomad FIN AF: 0.0796

Gnomad MID AF: 0.278

Gnomad NFE AF: 0.203

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.146 AC: 22203 AN: 152146 Hom.: 2022 Cov.: 32 AF XY: 0.137 AC XY: 10199 AN XY: 74378

African (AFR) AF: 0.0710 AC: 2949 AN: 41508

American (AMR) AF: 0.173 AC: 2637 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.296 AC: 1027 AN: 3464

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5190

South Asian (SAS) AF: 0.0651 AC: 314 AN: 4824

European-Finnish (FIN) AF: 0.0796 AC: 842 AN: 10582

Middle Eastern (MID) AF: 0.272 AC: 80 AN: 294

European-Non Finnish (NFE) AF: 0.203 AC: 13780 AN: 67976

Other (OTH) AF: 0.200 AC: 422 AN: 2112

Alfa AF: 0.151 Hom.: 1278

Bravo AF: 0.150

Asia WGS AF: 0.0450 AC: 156 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.75
PhyloP100		-0.16
Mutation Taster		=100/0	polymorphism (auto)

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: rs10487590; hg19: chr7-7277263;