rs3916898

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_000400.4(ERCC2):​c.*557T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0599 in 1,613,514 control chromosomes in the GnomAD database, including 3,180 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 0.049 ( 190 hom., cov: 31)
Exomes 𝑓: 0.061 ( 2990 hom. )

Consequence

ERCC2
NM_000400.4 3_prime_UTR

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.0940
Variant links:
Genes affected
ERCC2 (HGNC:3434): (ERCC excision repair 2, TFIIH core complex helicase subunit) The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
KLC3 (HGNC:20717): (kinesin light chain 3) This gene encodes a member of the kinesin light chain gene family. Kinesins are molecular motors involved in the transport of cargo along microtubules, and are composed of two kinesin heavy chain (KHC) and two kinesin light chain (KLC) molecules. KLCs are thought to typically be involved in binding cargo and regulating kinesin activity. In the rat, a protein similar to this gene product is expressed in post-meiotic spermatids, where it associates with structural components of sperm tails and mitochondria. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.9).
BA1
GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.062 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
ERCC2NM_000400.4 linkuse as main transcriptc.*557T>G 3_prime_UTR_variant 23/23 ENST00000391945.10 NP_000391.1 P18074-1
KLC3NM_177417.3 linkuse as main transcriptc.1443+55A>C intron_variant ENST00000391946.7 NP_803136.2 Q6P597-1A0A024R0V3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
ERCC2ENST00000391945 linkuse as main transcriptc.*557T>G 3_prime_UTR_variant 23/231 NM_000400.4 ENSP00000375809.4 P18074-1
KLC3ENST00000391946.7 linkuse as main transcriptc.1443+55A>C intron_variant 1 NM_177417.3 ENSP00000375810.2 Q6P597-1

Frequencies

GnomAD3 genomes
AF:
0.0485
AC:
7379
AN:
152088
Hom.:
189
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0358
Gnomad AMI
AF:
0.0175
Gnomad AMR
AF:
0.0341
Gnomad ASJ
AF:
0.0502
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.0483
Gnomad FIN
AF:
0.0454
Gnomad MID
AF:
0.101
Gnomad NFE
AF:
0.0635
Gnomad OTH
AF:
0.0561
GnomAD4 exome
AF:
0.0610
AC:
89205
AN:
1461308
Hom.:
2990
Cov.:
34
AF XY:
0.0609
AC XY:
44263
AN XY:
726896
show subpopulations
Gnomad4 AFR exome
AF:
0.0361
Gnomad4 AMR exome
AF:
0.0272
Gnomad4 ASJ exome
AF:
0.0576
Gnomad4 EAS exome
AF:
0.000176
Gnomad4 SAS exome
AF:
0.0517
Gnomad4 FIN exome
AF:
0.0510
Gnomad4 NFE exome
AF:
0.0667
Gnomad4 OTH exome
AF:
0.0603
GnomAD4 genome
AF:
0.0485
AC:
7387
AN:
152206
Hom.:
190
Cov.:
31
AF XY:
0.0472
AC XY:
3515
AN XY:
74432
show subpopulations
Gnomad4 AFR
AF:
0.0360
Gnomad4 AMR
AF:
0.0340
Gnomad4 ASJ
AF:
0.0502
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.0484
Gnomad4 FIN
AF:
0.0454
Gnomad4 NFE
AF:
0.0636
Gnomad4 OTH
AF:
0.0556
Alfa
AF:
0.0256
Hom.:
15
Bravo
AF:
0.0476
Asia WGS
AF:
0.0200
AC:
72
AN:
3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.90
CADD
Benign
0.26
DANN
Benign
0.45
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs3916898; hg19: chr19-45854330; API