rs3212951

Variant names:

• chr19-45420780-G-A
• rs3212951
• NM_001983.4:c.322-353C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-45420780-G-A
• chr19-45420780-G-C

Variant summary

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

The NM_001983.4(ERCC1):​c.322-353C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0192 in 152,054 control chromosomes in the GnomAD database, including 144 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.019 (144 hom., cov: 31)
• Consequence: ERCC1 NM_001983.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05
• Publications: 2 publications found

Genes affected

ERCC1 (HGNC:3433): (ERCC excision repair 1, endonuclease non-catalytic subunit) The product of this gene functions in the nucleotide excision repair pathway, and is required for the repair of DNA lesions such as those induced by UV light or formed by electrophilic compounds including cisplatin. The encoded protein forms a heterodimer with the XPF endonuclease (also known as ERCC4), and the heterodimeric endonuclease catalyzes the 5' incision in the process of excising the DNA lesion. The heterodimeric endonuclease is also involved in recombinational DNA repair and in the repair of inter-strand crosslinks. Mutations in this gene result in cerebrooculofacioskeletal syndrome, and polymorphisms that alter expression of this gene may play a role in carcinogenesis. Multiple transcript variants encoding different isoforms have been found for this gene. The last exon of this gene overlaps with the CD3e molecule, epsilon associated protein gene on the opposite strand. [provided by RefSeq, Oct 2009]

ERCC1 Gene-Disease associations (from GenCC):

• cerebrooculofacioskeletal syndrome 4

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Genomics England PanelApp, G2P
• Cockayne syndrome type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• COFS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ERCC1	NM_001983.4	c.322-353C>T		intron_variant	Intron 3 of 9	ENST00000300853.8	NP_001974.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
ERCC1	ENST00000300853.8	c.322-353C>T		intron_variant	Intron 3 of 9	1	NM_001983.4	ENSP00000300853.3

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2917 AN: 151936 Hom.: 144 Cov.: 31

Gnomad AFR AF: 0.00428

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0875

Gnomad ASJ AF: 0.00288

Gnomad EAS AF: 0.163

Gnomad SAS AF: 0.0170

Gnomad FIN AF: 0.0148

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.00406

Gnomad OTH AF: 0.0197

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0192 AC: 2921 AN: 152054 Hom.: 144 Cov.: 31 AF XY: 0.0222 AC XY: 1648 AN XY: 74322

African (AFR) AF: 0.00426 AC: 177 AN: 41504

American (AMR) AF: 0.0877 AC: 1335 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.00288 AC: 10 AN: 3470

East Asian (EAS) AF: 0.164 AC: 844 AN: 5142

South Asian (SAS) AF: 0.0170 AC: 82 AN: 4820

European-Finnish (FIN) AF: 0.0148 AC: 157 AN: 10590

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

European-Non Finnish (NFE) AF: 0.00406 AC: 276 AN: 67996

Other (OTH) AF: 0.0190 AC: 40 AN: 2104

Alfa AF: 0.0104 Hom.: 18

Bravo AF: 0.0265

Asia WGS AF: 0.0750 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.53
DANN	Benign	0.34
PhyloP100		-1.1
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: rs3212951; hg19: chr19-45924038;