14-54538371-G-T

Variant names:

• chr14-54538371-G-T
• rs142726606
• NM_006568.3:c.987G>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Strong BP7

The NM_006568.3(CGRRF1):​c.987G>T​(p.Pro329Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000688 in 1,454,360 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. P329P) has been classified as Benign.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: CGRRF1 NM_006568.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.537
• Publications: 0 publications found

Genes affected

CGRRF1 (HGNC:15528): (cell growth regulator with ring finger domain 1) Predicted to enable metal ion binding activity. Predicted to be involved in negative regulation of cell growth. Located in endoplasmic reticulum and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP7: Synonymous conserved (PhyloP=0.537 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_006568.3. 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
	CGRRF1	NM_006568.3	MANE Select	c.987G>T	p.Pro329Pro	synonymous	Exon 6 of 6	NP_006559.1	Q99675

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CGRRF1	ENST00000216420.12	TSL:1 MANE Select	c.987G>T	p.Pro329Pro	synonymous	Exon 6 of 6	ENSP00000216420.7	Q99675
	CGRRF1	ENST00000908184.1		c.1122G>T	p.Pro374Pro	synonymous	Exon 8 of 8	ENSP00000578243.1
	CGRRF1	ENST00000908185.1		c.1080G>T	p.Pro360Pro	synonymous	Exon 7 of 7	ENSP00000578244.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.88e-7 AC: 1 AN: 1454360 Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1 AN XY: 721920

African (AFR) AF: 0.00 AC: 0 AN: 33340

American (AMR) AF: 0.00 AC: 0 AN: 44514

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26002

East Asian (EAS) AF: 0.00 AC: 0 AN: 39482

South Asian (SAS) AF: 0.00 AC: 0 AN: 86028

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53280

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5748

European-Non Finnish (NFE) AF: 9.04e-7 AC: 1 AN: 1105890

Other (OTH) AF: 0.00 AC: 0 AN: 60076

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	2.4
DANN	Benign	0.46
PhyloP100		0.54

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: rs142726606; hg19: chr14-55005089;