2-27112718-T-C

Variant names:

• chr2-27112718-T-C
• rs1866559
• NM_006569.6:c.-12+6128A>G

Variant summary

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

The NM_006569.6(CGREF1):​c.-12+6128A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.328 in 152,150 control chromosomes in the GnomAD database, including 9,065 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 0.33 (9065 hom., cov: 33)
• Consequence: CGREF1 NM_006569.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0170
• Publications: 11 publications found

Genes affected

CGREF1 (HGNC:16962): (cell growth regulator with EF-hand domain 1) Predicted to enable calcium ion binding activity. Predicted to be involved in negative regulation of cell population proliferation. Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

LOC124907744 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.486 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006569.6. 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
	CGREF1	NM_006569.6	MANE Select	c.-12+6128A>G		intron	N/A	NP_006560.3
	CGREF1	NM_001166239.2		c.-12+6057A>G		intron	N/A	NP_001159711.1	Q99674-4
	CGREF1	NM_001166240.2		c.-12+6128A>G		intron	N/A	NP_001159712.1	Q99674-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGREF1	ENST00000402394.6	TSL:2 MANE Select	c.-12+6128A>G		intron	N/A	ENSP00000385452.1	Q99674-4
	CGREF1	ENST00000312734.8	TSL:5	c.-307-1750A>G		intron	N/A	ENSP00000324025.4	Q99674-4
	CGREF1	ENST00000405600.5	TSL:4	c.-12+6057A>G		intron	N/A	ENSP00000386113.1	Q99674-4

Frequencies

GnomAD3 genomes AF: 0.328 AC: 49878 AN: 152032 Hom.: 9050 Cov.: 33

Gnomad AFR AF: 0.191

Gnomad AMI AF: 0.522

Gnomad AMR AF: 0.495

Gnomad ASJ AF: 0.392

Gnomad EAS AF: 0.241

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.335

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.374

Gnomad OTH AF: 0.344

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

GnomAD4 genome AF: 0.328 AC: 49906 AN: 152150 Hom.: 9065 Cov.: 33 AF XY: 0.329 AC XY: 24469 AN XY: 74380

African (AFR) AF: 0.191 AC: 7921 AN: 41520

American (AMR) AF: 0.495 AC: 7572 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.392 AC: 1360 AN: 3470

East Asian (EAS) AF: 0.240 AC: 1246 AN: 5184

South Asian (SAS) AF: 0.313 AC: 1509 AN: 4824

European-Finnish (FIN) AF: 0.335 AC: 3547 AN: 10576

Middle Eastern (MID) AF: 0.330 AC: 97 AN: 294

European-Non Finnish (NFE) AF: 0.374 AC: 25441 AN: 67972

Other (OTH) AF: 0.349 AC: 737 AN: 2112

Alfa AF: 0.367 Hom.: 13795

Bravo AF: 0.340

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.72
PhyloP100		-0.017
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: rs1866559; hg19: chr2-27335586;