rs16979802

Variant names:

• chr19-45416697-G-C
• rs16979802
• NM_001983.4:c.602+124C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-45416697-G-C
• chr19-45416697-G-A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001983.4(ERCC1):​c.602+124C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0804 in 727,248 control chromosomes in the GnomAD database, including 2,954 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.067 (444 hom., cov: 31)
  • Exomes 𝑓: 0.084 (2510 hom.)
• Consequence: ERCC1 NM_001983.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.461
• Publications: 6 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: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P, Genomics England PanelApp
• 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 19-45416697-G-C is Benign according to our data. Variant chr19-45416697-G-C is described in ClinVar as Benign. ClinVar VariationId is 1245816.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001983.4. 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
	ERCC1	NM_001983.4	MANE Select	c.602+124C>G		intron	N/A	NP_001974.1	P07992-1
	ERCC1	NM_001369408.1		c.602+124C>G		intron	N/A	NP_001356337.1	P07992-3
	ERCC1	NM_001369409.1		c.602+124C>G		intron	N/A	NP_001356338.1	P07992-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC1	ENST00000300853.8	TSL:1 MANE Select	c.602+124C>G		intron	N/A	ENSP00000300853.3	P07992-1
	ERCC1	ENST00000013807.9	TSL:1	c.602+124C>G		intron	N/A	ENSP00000013807.4	P07992-3
	ERCC1	ENST00000340192.11	TSL:1	c.602+124C>G		intron	N/A	ENSP00000345203.6	P07992-2

Frequencies

GnomAD3 genomes AF: 0.0674 AC: 10210 AN: 151550 Hom.: 445 Cov.: 31

Gnomad AFR AF: 0.0305

Gnomad AMI AF: 0.107

Gnomad AMR AF: 0.0737

Gnomad ASJ AF: 0.0885

Gnomad EAS AF: 0.230

Gnomad SAS AF: 0.0959

Gnomad FIN AF: 0.0546

Gnomad MID AF: 0.142

Gnomad NFE AF: 0.0738

Gnomad OTH AF: 0.0774

GnomAD4 exome AF: 0.0839 AC: 48290 AN: 575580 Hom.: 2510 Cov.: 7 AF XY: 0.0850 AC XY: 26210 AN XY: 308382

African (AFR) AF: 0.0320 AC: 517 AN: 16140

American (AMR) AF: 0.0779 AC: 2405 AN: 30878

Ashkenazi Jewish (ASJ) AF: 0.0937 AC: 1785 AN: 19044

East Asian (EAS) AF: 0.219 AC: 7332 AN: 33464

South Asian (SAS) AF: 0.0926 AC: 5697 AN: 61538

European-Finnish (FIN) AF: 0.0570 AC: 2487 AN: 43610

Middle Eastern (MID) AF: 0.109 AC: 271 AN: 2496

European-Non Finnish (NFE) AF: 0.0750 AC: 25328 AN: 337536

Other (OTH) AF: 0.0799 AC: 2468 AN: 30874

GnomAD4 genome AF: 0.0673 AC: 10202 AN: 151668 Hom.: 444 Cov.: 31 AF XY: 0.0678 AC XY: 5027 AN XY: 74118

African (AFR) AF: 0.0304 AC: 1259 AN: 41404

American (AMR) AF: 0.0738 AC: 1122 AN: 15212

Ashkenazi Jewish (ASJ) AF: 0.0885 AC: 307 AN: 3468

East Asian (EAS) AF: 0.229 AC: 1169 AN: 5114

South Asian (SAS) AF: 0.0963 AC: 463 AN: 4806

European-Finnish (FIN) AF: 0.0546 AC: 571 AN: 10464

Middle Eastern (MID) AF: 0.143 AC: 42 AN: 294

European-Non Finnish (NFE) AF: 0.0738 AC: 5012 AN: 67900

Other (OTH) AF: 0.0761 AC: 160 AN: 2102

Alfa AF: 0.0610 Hom.: 40

Bravo AF: 0.0662

Asia WGS AF: 0.127 AC: 439 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
BayesDel_noAF	Benign	-0.78
CADD	Benign	8.9
DANN	Benign	0.77
PhyloP100		0.46
PromoterAI		0.0031	Neutral
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: rs16979802; hg19: chr19-45919955; COSMIC: COSV50005117; COSMIC: COSV50005117;