rs7259723

Variant names:

• chr19-17555827-C-T
• rs7259723
• NM_024656.4:c.114C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-17555827-C-T
• chr19-17555827-C-G

Variant summary

Our verdict is Benign. The variant received -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_024656.4(COLGALT1):​c.114C>T​(p.Phe38Phe) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.534 in 1,298,894 control chromosomes in the GnomAD database, including 192,087 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.44 (16699 hom., cov: 33)
  • Exomes 𝑓: 0.55 (175388 hom.)
• Consequence: COLGALT1 NM_024656.4 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.618
• Publications: 11 publications found

Genes affected

COLGALT1 (HGNC:26182): (collagen beta(1-O)galactosyltransferase 1) The protein encoded by this gene is one of two enzymes that transfers galactose moieties to hydroxylysine residues of collagen and mannose binding lectin. This gene is constitutively expressed and encodes a soluble protein that localizes to the endoplasmic reticulum. [provided by RefSeq, Dec 2015]

COLGALT1 Gene-Disease associations (from GenCC):

• brain small vessel disease 3

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, ClinGen, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.48).
• BP6: Variant 19-17555827-C-T is Benign according to our data. Variant chr19-17555827-C-T is described in ClinVar as Benign. ClinVar VariationId is 1924834.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.618 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.558 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024656.4. 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
	COLGALT1	NM_024656.4	MANE Select	c.114C>T	p.Phe38Phe	synonymous	Exon 1 of 12	NP_078932.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	COLGALT1	ENST00000252599.9	TSL:1 MANE Select	c.114C>T	p.Phe38Phe	synonymous	Exon 1 of 12	ENSP00000252599.3	Q8NBJ5
	COLGALT1	ENST00000886053.1		c.114C>T	p.Phe38Phe	synonymous	Exon 1 of 13	ENSP00000556112.1
	COLGALT1	ENST00000886054.1		c.114C>T	p.Phe38Phe	synonymous	Exon 1 of 14	ENSP00000556113.1

Frequencies

GnomAD3 genomes AF: 0.440 AC: 66555 AN: 151328 Hom.: 16700 Cov.: 33

Gnomad AFR AF: 0.206

Gnomad AMI AF: 0.448

Gnomad AMR AF: 0.425

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.352

Gnomad SAS AF: 0.429

Gnomad FIN AF: 0.561

Gnomad MID AF: 0.573

Gnomad NFE AF: 0.563

Gnomad OTH AF: 0.492

GnomAD2 exomes AF: 0.491 AC: 10728 AN: 21858 AF XY: 0.493

Gnomad AFR exome AF: 0.174

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.603

Gnomad EAS exome AF: 0.354

Gnomad FIN exome AF: 0.561

Gnomad NFE exome AF: 0.553

Gnomad OTH exome AF: 0.515

GnomAD4 exome AF: 0.547 AC: 627095 AN: 1147458 Hom.: 175388 Cov.: 45 AF XY: 0.546 AC XY: 302608 AN XY: 554214

African (AFR) AF: 0.182 AC: 4287 AN: 23596

American (AMR) AF: 0.365 AC: 4141 AN: 11340

Ashkenazi Jewish (ASJ) AF: 0.612 AC: 10213 AN: 16682

East Asian (EAS) AF: 0.301 AC: 7988 AN: 26578

South Asian (SAS) AF: 0.442 AC: 18299 AN: 41436

European-Finnish (FIN) AF: 0.552 AC: 13976 AN: 25324

Middle Eastern (MID) AF: 0.586 AC: 1835 AN: 3130

European-Non Finnish (NFE) AF: 0.569 AC: 542321 AN: 953436

Other (OTH) AF: 0.523 AC: 24035 AN: 45936

GnomAD4 genome AF: 0.440 AC: 66562 AN: 151436 Hom.: 16699 Cov.: 33 AF XY: 0.438 AC XY: 32377 AN XY: 73982

African (AFR) AF: 0.205 AC: 8515 AN: 41466

American (AMR) AF: 0.424 AC: 6448 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.633 AC: 2193 AN: 3464

East Asian (EAS) AF: 0.352 AC: 1811 AN: 5148

South Asian (SAS) AF: 0.430 AC: 2070 AN: 4818

European-Finnish (FIN) AF: 0.561 AC: 5783 AN: 10312

Middle Eastern (MID) AF: 0.582 AC: 170 AN: 292

European-Non Finnish (NFE) AF: 0.563 AC: 38125 AN: 67740

Other (OTH) AF: 0.496 AC: 1042 AN: 2100

Alfa AF: 0.480 Hom.: 2251

Bravo AF: 0.422

Asia WGS AF: 0.375 AC: 1296 AN: 3452

ClinVar

ClinVar submissions

Significance: 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	-0.48
CADD	Benign	13
DANN	Benign	0.97
PhyloP100		0.62
PromoterAI		-0.075	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
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: rs7259723; hg19: chr19-17666636; COSMIC: COSV53108722; COSMIC: COSV53108722;