1-74599757-C-T

Variant names:

• chr1-74599757-C-T
• rs696698
• NM_001002912.5:c.1664G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001002912.5(ERICH3):​c.1664G>A​(p.Arg555His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0448 in 1,611,980 control chromosomes in the GnomAD database, including 2,416 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R555C) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.064 (401 hom., cov: 32)
  • Exomes 𝑓: 0.043 (2015 hom.)
• Consequence: ERICH3 NM_001002912.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0480
• Publications: 15 publications found

Genes affected

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

ERICH3-AS1 (HGNC:41093): (ERICH3 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0015816092).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001002912.5. 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
	ERICH3	NM_001002912.5	MANE Select	c.1664G>A	p.Arg555His	missense	Exon 11 of 15	NP_001002912.4
	ERICH3-AS1	NR_121670.1		n.173+9850C>T		intron	N/A
	ERICH3-AS1	NR_121671.1		n.81-15449C>T		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERICH3	ENST00000326665.10	TSL:5 MANE Select	c.1664G>A	p.Arg555His	missense	Exon 11 of 15	ENSP00000322609.5	Q5RHP9-1
	ERICH3	ENST00000420661.6	TSL:1	c.1073G>A	p.Arg358His	missense	Exon 6 of 7	ENSP00000398581.2	Q5RHP9-3
	ERICH3-AS1	ENST00000612390.4	TSL:1	n.81-15449C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0642 AC: 9739 AN: 151706 Hom.: 400 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.0492

Gnomad ASJ AF: 0.0511

Gnomad EAS AF: 0.0608

Gnomad SAS AF: 0.131

Gnomad FIN AF: 0.0528

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.0352

Gnomad OTH AF: 0.0600

GnomAD2 exomes AF: 0.0617 AC: 15441 AN: 250348 AF XY: 0.0622

Gnomad AFR exome AF: 0.119

Gnomad AMR exome AF: 0.0683

Gnomad ASJ exome AF: 0.0548

Gnomad EAS exome AF: 0.0527

Gnomad FIN exome AF: 0.0575

Gnomad NFE exome AF: 0.0371

Gnomad OTH exome AF: 0.0527

GnomAD4 exome AF: 0.0428 AC: 62485 AN: 1460156 Hom.: 2015 Cov.: 31 AF XY: 0.0450 AC XY: 32710 AN XY: 726428

African (AFR) AF: 0.123 AC: 4105 AN: 33344

American (AMR) AF: 0.0662 AC: 2948 AN: 44550

Ashkenazi Jewish (ASJ) AF: 0.0516 AC: 1343 AN: 26038

East Asian (EAS) AF: 0.0695 AC: 2759 AN: 39670

South Asian (SAS) AF: 0.122 AC: 10468 AN: 86118

European-Finnish (FIN) AF: 0.0573 AC: 3058 AN: 53382

Middle Eastern (MID) AF: 0.0537 AC: 309 AN: 5752

European-Non Finnish (NFE) AF: 0.0310 AC: 34424 AN: 1111006

Other (OTH) AF: 0.0509 AC: 3071 AN: 60296

GnomAD4 genome AF: 0.0643 AC: 9759 AN: 151824 Hom.: 401 Cov.: 32 AF XY: 0.0663 AC XY: 4918 AN XY: 74202

African (AFR) AF: 0.116 AC: 4805 AN: 41448

American (AMR) AF: 0.0492 AC: 748 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0511 AC: 177 AN: 3466

East Asian (EAS) AF: 0.0606 AC: 311 AN: 5136

South Asian (SAS) AF: 0.131 AC: 629 AN: 4812

European-Finnish (FIN) AF: 0.0528 AC: 559 AN: 10596

Middle Eastern (MID) AF: 0.0544 AC: 16 AN: 294

European-Non Finnish (NFE) AF: 0.0352 AC: 2388 AN: 67844

Other (OTH) AF: 0.0585 AC: 123 AN: 2104

Alfa AF: 0.0441 Hom.: 912

Bravo AF: 0.0647

TwinsUK AF: 0.0237 AC: 88

ALSPAC AF: 0.0301 AC: 116

ESP6500AA AF: 0.105 AC: 462

ESP6500EA AF: 0.0345 AC: 297

ExAC AF: 0.0638 AC: 7750

Asia WGS AF: 0.107 AC: 371 AN: 3478

EpiCase AF: 0.0362

EpiControl AF: 0.0379

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.83	T
BayesDel_noAF	Benign	-0.86
CADD	Benign	1.8
DANN	Benign	0.42
DEOGEN2	Benign	0.0033	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.0080	N
LIST_S2	Benign	0.18	T
MetaRNN	Benign	0.0016	T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.048
PROVEAN	Benign	1.3	N
REVEL	Benign	0.050
Sift	Benign	0.28	T
Sift4G	Benign	0.24	T
Polyphen		0.0	B
Vest4		0.088
MPC		0.018
ClinPred		0.00045	T
GERP RS		-1.3
Varity_R		0.022
gMVP		0.018
Mutation Taster		=100/0	polymorphism (auto)

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: rs696698; hg19: chr1-75065441; COSMIC: COSV58607545;