rs34839928

Variant names:

• chr14-54531033-C-T
• rs34839928
• NM_006568.3:c.553C>T

Your query was ambiguous. Multiple possible variants found:

• chr14-54531033-C-T
• chr14-54531033-C-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BS1 BS2

The NM_006568.3(CGRRF1):​c.553C>T​(p.Arg185Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00878 in 1,608,624 control chromosomes in the GnomAD database, including 96 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0075 (11 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (85 hom.)
• Consequence: CGRRF1 NM_006568.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 2.77
• Publications: 12 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006599784).
• BP6: Variant 14-54531033-C-T is Benign according to our data. Variant chr14-54531033-C-T is described in ClinVar as Benign. ClinVar VariationId is 710468.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS1: Variant frequency is greater than expected in population amr. GnomAd4 allele frequency = 0.00748 (1138/152078) while in subpopulation AMR AF = 0.0189 (288/15268). AF 95% confidence interval is 0.0171. There are 11 homozygotes in GnomAd4. There are 553 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 11 AR gene

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.553C>T	p.Arg185Trp	missense	Exon 4 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.553C>T	p.Arg185Trp	missense	Exon 4 of 6	ENSP00000216420.7	Q99675
	CGRRF1	ENST00000908184.1		c.688C>T	p.Arg230Trp	missense	Exon 6 of 8	ENSP00000578243.1
	CGRRF1	ENST00000908185.1		c.646C>T	p.Arg216Trp	missense	Exon 5 of 7	ENSP00000578244.1

Frequencies

GnomAD3 genomes AF: 0.00751 AC: 1141 AN: 151964 Hom.: 11 Cov.: 32

Gnomad AFR AF: 0.00213

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0189

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00284

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0158

GnomAD2 exomes AF: 0.00693 AC: 1703 AN: 245854 AF XY: 0.00732

Gnomad AFR exome AF: 0.00218

Gnomad AMR exome AF: 0.00911

Gnomad ASJ exome AF: 0.000808

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00362

Gnomad NFE exome AF: 0.0100

Gnomad OTH exome AF: 0.0103

GnomAD4 exome AF: 0.00891 AC: 12978 AN: 1456546 Hom.: 85 Cov.: 30 AF XY: 0.00886 AC XY: 6418 AN XY: 724414

African (AFR) AF: 0.00256 AC: 85 AN: 33220

American (AMR) AF: 0.0102 AC: 446 AN: 43584

Ashkenazi Jewish (ASJ) AF: 0.00104 AC: 27 AN: 26010

East Asian (EAS) AF: 0.000126 AC: 5 AN: 39602

South Asian (SAS) AF: 0.00298 AC: 253 AN: 84976

European-Finnish (FIN) AF: 0.00443 AC: 236 AN: 53326

Middle Eastern (MID) AF: 0.0125 AC: 72 AN: 5752

European-Non Finnish (NFE) AF: 0.0101 AC: 11234 AN: 1109874

Other (OTH) AF: 0.0103 AC: 620 AN: 60202

GnomAD4 genome AF: 0.00748 AC: 1138 AN: 152078 Hom.: 11 Cov.: 32 AF XY: 0.00744 AC XY: 553 AN XY: 74338

African (AFR) AF: 0.00212 AC: 88 AN: 41516

American (AMR) AF: 0.0189 AC: 288 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4812

European-Finnish (FIN) AF: 0.00284 AC: 30 AN: 10578

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0100 AC: 681 AN: 67936

Other (OTH) AF: 0.0156 AC: 33 AN: 2112

Alfa AF: 0.00959 Hom.: 36

Bravo AF: 0.00852

TwinsUK AF: 0.00728 AC: 27

ALSPAC AF: 0.0104 AC: 40

ESP6500AA AF: 0.00182 AC: 8

ESP6500EA AF: 0.0105 AC: 90

ExAC AF: 0.00693 AC: 841

Asia WGS AF: 0.000867 AC: 3 AN: 3476

EpiCase AF: 0.0129

EpiControl AF: 0.0119

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.41
CADD	Pathogenic	27
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.076	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Uncertain	0.87	D
MetaRNN	Benign	0.0066	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.8	L
PhyloP100		2.8
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-2.3	N
REVEL	Benign	0.10
Sift	Uncertain	0.014	D
Sift4G	Uncertain	0.019	D
Polyphen		1.0	D
Vest4		0.66
MVP		0.42
MPC		0.45
ClinPred		0.055	T
GERP RS		4.6
Varity_R		0.11
gMVP		0.63
Mutation Taster		=82/18	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.18		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: rs34839928; hg19: chr14-54997751; COSMIC: COSV53596934; COSMIC: COSV53596934;