7-7237632-G-T

Position:

• chr7-7237632-G-T

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
C1GALT1	NM_020156.5	c.221-623G>T		intron_variant		ENST00000436587.7	NP_064541.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
C1GALT1	ENST00000436587.7	c.221-623G>T		intron_variant		5	NM_020156.5	ENSP00000389176	P1
C1GALT1	ENST00000223122.4	c.221-623G>T		intron_variant		1		ENSP00000223122	P1
C1GALT1	ENST00000402468.3	c.221-623G>T		intron_variant		1		ENSP00000384550
C1GALT1	ENST00000429911.5	c.221-623G>T		intron_variant		5		ENSP00000407666

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

Gnomad4 AFR AF: 0.0710

Gnomad4 AMR AF: 0.173

Gnomad4 ASJ AF: 0.296

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.0651

Gnomad4 FIN AF: 0.0796

Gnomad4 NFE AF: 0.203

Gnomad4 OTH AF: 0.200

Alfa AF: 0.159 Hom.: 1090

Bravo AF: 0.150

Asia WGS AF: 0.0450 AC: 156 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	2.1
DANN	Benign	0.75

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

Publications

LitVar

Other links and lift over

dbSNP: rs10487590; hg19: chr7-7277263;