2-27112718-T-C

Position:

• chr2-27112718-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CGREF1	NM_006569.6	c.-12+6128A>G		intron_variant		ENST00000402394.6	NP_006560.3
LOC124907744	XR_007086252.1	n.401-1906T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CGREF1	ENST00000402394.6	c.-12+6128A>G		intron_variant		2	NM_006569.6	ENSP00000385452	A2

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

Gnomad4 AFR AF: 0.191

Gnomad4 AMR AF: 0.495

Gnomad4 ASJ AF: 0.392

Gnomad4 EAS AF: 0.240

Gnomad4 SAS AF: 0.313

Gnomad4 FIN AF: 0.335

Gnomad4 NFE AF: 0.374

Gnomad4 OTH AF: 0.349

Alfa AF: 0.371 Hom.: 10845

Bravo AF: 0.340

Asia WGS AF: 0.303 AC: 1054 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.4
DANN	Benign	0.72

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: rs1866559; hg19: chr2-27335586;