rs1007616

Variant names:

• chr19-45409835-T-C
• rs1007616
• NM_012099.3:c.*334T>C

Your query was ambiguous. Multiple possible variants found:

• chr19-45409835-T-C
• chr19-45409835-T-A
• chr19-45409835-T-G

Variant summary

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

The NM_012099.3(POLR1G):​c.*334T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.457 in 697,704 control chromosomes in the GnomAD database, including 78,446 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.49 (19099 hom., cov: 29)
  • Exomes 𝑓: 0.45 (59347 hom.)
• Consequence: POLR1G NM_012099.3 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.198
• Publications: 23 publications found

Genes affected

POLR1G (HGNC:24219): (RNA polymerase I subunit G) Enables RNA binding activity. Predicted to be involved in transmembrane receptor protein tyrosine kinase signaling pathway. Predicted to act upstream of or within rRNA transcription. Located in cytosol; mitochondrion; and nuclear lumen. [provided by Alliance of Genome Resources, Apr 2022]

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=-0.83).
• BP6: Variant 19-45409835-T-C is Benign according to our data. Variant chr19-45409835-T-C is described in ClinVar as Benign. ClinVar VariationId is 1275555.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.732 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_012099.3. 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
	POLR1G	NM_012099.3	MANE Select	c.*334T>C		3_prime_UTR	Exon 3 of 3	NP_036231.1	O15446-1
	ERCC1	NM_001983.4	MANE Select	c.844-110A>G		intron	N/A	NP_001974.1	P07992-1
	POLR1G	NM_001297590.3		c.*334T>C		3_prime_UTR	Exon 3 of 3	NP_001284519.1	O15446-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	POLR1G	ENST00000309424.8	TSL:1 MANE Select	c.*334T>C		3_prime_UTR	Exon 3 of 3	ENSP00000310966.3	O15446-1
	ERCC1	ENST00000300853.8	TSL:1 MANE Select	c.844-110A>G		intron	N/A	ENSP00000300853.3	P07992-1
	ERCC1	ENST00000340192.11	TSL:1	c.772-110A>G		intron	N/A	ENSP00000345203.6	P07992-2

Frequencies

GnomAD3 genomes AF: 0.486 AC: 73232 AN: 150610 Hom.: 19075 Cov.: 29

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.567

Gnomad ASJ AF: 0.385

Gnomad EAS AF: 0.752

Gnomad SAS AF: 0.578

Gnomad FIN AF: 0.361

Gnomad MID AF: 0.430

Gnomad NFE AF: 0.383

Gnomad OTH AF: 0.473

GnomAD4 exome AF: 0.449 AC: 245715 AN: 546986 Hom.: 59347 Cov.: 0 AF XY: 0.453 AC XY: 133607 AN XY: 295052

African (AFR) AF: 0.614 AC: 9204 AN: 14994

American (AMR) AF: 0.663 AC: 21466 AN: 32366

Ashkenazi Jewish (ASJ) AF: 0.386 AC: 7455 AN: 19326

East Asian (EAS) AF: 0.722 AC: 22859 AN: 31646

South Asian (SAS) AF: 0.568 AC: 34525 AN: 60798

European-Finnish (FIN) AF: 0.373 AC: 17654 AN: 47276

Middle Eastern (MID) AF: 0.437 AC: 1034 AN: 2364

European-Non Finnish (NFE) AF: 0.383 AC: 118171 AN: 308550

Other (OTH) AF: 0.450 AC: 13347 AN: 29666

GnomAD4 genome AF: 0.486 AC: 73302 AN: 150718 Hom.: 19099 Cov.: 29 AF XY: 0.489 AC XY: 35980 AN XY: 73520

African (AFR) AF: 0.624 AC: 25613 AN: 41028

American (AMR) AF: 0.567 AC: 8578 AN: 15122

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 1337 AN: 3470

East Asian (EAS) AF: 0.752 AC: 3874 AN: 5150

South Asian (SAS) AF: 0.576 AC: 2750 AN: 4772

European-Finnish (FIN) AF: 0.361 AC: 3676 AN: 10196

Middle Eastern (MID) AF: 0.432 AC: 127 AN: 294

European-Non Finnish (NFE) AF: 0.383 AC: 25919 AN: 67686

Other (OTH) AF: 0.476 AC: 996 AN: 2092

Alfa AF: 0.409 Hom.: 2502

Bravo AF: 0.508

Asia WGS AF: 0.659 AC: 2293 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	-0.83
CADD	Benign	2.7
DANN	Benign	0.84
PhyloP100		-0.20
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: rs1007616; hg19: chr19-45913093;