NM_018948.4:c.716C>T

Variant names:

• chr1-8013883-G-A
• rs116791613
• NM_018948.4:c.716C>T

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_018948.4(ERRFI1):​c.716C>T​(p.Pro239Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00072 in 1,614,102 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0038 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00040 (4 hom.)
• Consequence: ERRFI1 NM_018948.4 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.402
• Publications: 3 publications found

Genes affected

ERRFI1 (HGNC:18185): (ERBB receptor feedback inhibitor 1) ERRFI1 is a cytoplasmic protein whose expression is upregulated with cell growth (Wick et al., 1995 [PubMed 7641805]). It shares significant homology with the protein product of rat gene-33, which is induced during cell stress and mediates cell signaling (Makkinje et al., 2000 [PubMed 10749885]; Fiorentino et al., 2000 [PubMed 11003669]).[supplied by OMIM, Mar 2008]

ACMG classification

Our verdict: Benign. The variant received -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0036968887).
• BP6: Variant 1-8013883-G-A is Benign according to our data. Variant chr1-8013883-G-A is described in ClinVar as Benign. ClinVar VariationId is 710834.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomAd4 at 584 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018948.4. 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
	ERRFI1	NM_018948.4	MANE Select	c.716C>T	p.Pro239Leu	missense	Exon 4 of 4	NP_061821.1	I6S2Y9

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERRFI1	ENST00000377482.10	TSL:1 MANE Select	c.716C>T	p.Pro239Leu	missense	Exon 4 of 4	ENSP00000366702.5	Q9UJM3
	ERRFI1	ENST00000857115.1		c.716C>T	p.Pro239Leu	missense	Exon 5 of 5	ENSP00000527174.1
	ERRFI1	ENST00000857116.1		c.716C>T	p.Pro239Leu	missense	Exon 5 of 5	ENSP00000527175.1

Frequencies

GnomAD3 genomes AF: 0.00383 AC: 583 AN: 152154 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0131

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00183

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.00239

GnomAD2 exomes AF: 0.00118 AC: 296 AN: 251200 AF XY: 0.000891

Gnomad AFR exome AF: 0.0155

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000528

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.000395 AC: 578 AN: 1461830 Hom.: 4 Cov.: 31 AF XY: 0.000353 AC XY: 257 AN XY: 727216

African (AFR) AF: 0.0126 AC: 423 AN: 33480

American (AMR) AF: 0.00114 AC: 51 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86246

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53414

Middle Eastern (MID) AF: 0.00121 AC: 7 AN: 5768

European-Non Finnish (NFE) AF: 0.0000405 AC: 45 AN: 1111982

Other (OTH) AF: 0.000845 AC: 51 AN: 60390

GnomAD4 genome AF: 0.00384 AC: 584 AN: 152272 Hom.: 0 Cov.: 32 AF XY: 0.00356 AC XY: 265 AN XY: 74462

African (AFR) AF: 0.0130 AC: 542 AN: 41542

American (AMR) AF: 0.00183 AC: 28 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 68022

Other (OTH) AF: 0.00237 AC: 5 AN: 2110

Alfa AF: 0.00166 Hom.: 4

Bravo AF: 0.00484

ESP6500AA AF: 0.0172 AC: 76

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.00140 AC: 170

Asia WGS AF: 0.000289 AC: 1 AN: 3478

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	0.065
BayesDel_addAF	Benign	-0.64	T
BayesDel_noAF	Benign	-0.68
CADD	Benign	16
DANN	Benign	0.82
DEOGEN2	Benign	0.34	T
Eigen	Benign	-0.69
Eigen_PC	Benign	-0.64
FATHMM_MKL	Benign	0.37	N
LIST_S2	Benign	0.74	T
MetaRNN	Benign	0.0037	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	1.1	L
PhyloP100		0.40
PrimateAI	Benign	0.42	T
PROVEAN	Benign	-0.60	N
REVEL	Benign	0.018
Sift	Benign	0.11	T
Sift4G	Benign	0.30	T
Polyphen		0.0030	B
Vest4		0.18
MVP		0.32
MPC		0.18
ClinPred		0.0013	T
GERP RS		1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.7
Varity_R		0.032
gMVP		0.23
Mutation Taster		=98/2	polymorphism

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: rs116791613; hg19: chr1-8073943;