1-74571190-C-T

Position:

• chr1-74571190-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001002912.5(ERICH3):​c.4520G>A​(p.Arg1507Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,870 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: ERICH3 NM_001002912.5 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.47

Genes affected

ERICH3 (HGNC:25346): (glutamate rich 3)

ACMG classification

Verdict is Likely_benign. Variant got -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.028587133).
• BP6: Variant 1-74571190-C-T is Benign according to our data. Variant chr1-74571190-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2338731.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
ERICH3	NM_001002912.5	c.4520G>A	p.Arg1507Gln	missense_variant	14/15	ENST00000326665.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
ERICH3	ENST00000326665.10	c.4520G>A	p.Arg1507Gln	missense_variant	14/15	5	NM_001002912.5	P3
ERICH3	ENST00000433746.2	n.2662G>A		non_coding_transcript_exon_variant	2/3	1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461870 Hom.: 0 Cov.: 87 AF XY: 0.00000275 AC XY: 2 AN XY: 727242

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 21, 2022

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.062
BayesDel_addAF	Benign	-0.49	T
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.027
DANN	Benign	0.34
DEOGEN2	Benign	0.0044	T
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.0013	N
LIST_S2	Benign	0.46	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.029	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Benign	-1.0	N
MutationTaster	Benign	1.0	N
PROVEAN	Benign	0.19	N
REVEL	Benign	0.0040
Sift	Benign	1.0	T
Sift4G	Benign	0.51	T
Polyphen		0.0	B
Vest4		0.069
MutPred		0.15		Gain of methylation at K1509 (P = 0.1115);
MVP		0.092
MPC		0.018
ClinPred		0.022	T
GERP RS		-1.8
Varity_R		0.017
gMVP		0.023

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: rs762200675; hg19: chr1-75036874;