rs690528

Variant names:

• chr9-95876006-A-G
• rs690528
• NM_020207.7:c.-33A>G

Your query was ambiguous. Multiple possible variants found:

• chr9-95876006-A-G
• chr9-95876006-A-T

Variant summary

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

The NM_020207.7(ERCC6L2):​c.-33A>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,570,194 control chromosomes in the GnomAD database, including 73,488 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.26 (5846 hom., cov: 33)
  • Exomes 𝑓: 0.31 (67642 hom.)
• Consequence: ERCC6L2 NM_020207.7 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.0600
• Publications: 19 publications found

Genes affected

ERCC6L2 (HGNC:26922): (ERCC excision repair 6 like 2) This gene encodes a member of the Snf2 family of helicase-like proteins. The encoded protein may play a role in DNA repair and mitochondrial function. Mutations in this gene have been associated with bone marrow failure syndrome 2. Alternatively spliced transcript variants that encode different protein isoforms have been described. [provided by RefSeq, Apr 2014]

ERCC6L2-AS1 (HGNC:27858): (ERCC6L2 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=8.9636445E-4).
• BP6: Variant 9-95876006-A-G is Benign according to our data. Variant chr9-95876006-A-G is described in ClinVar as Benign. ClinVar VariationId is 1165173.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.356 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020207.7. 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
	ERCC6L2	NM_020207.7	MANE Select	c.-33A>G		5_prime_UTR	Exon 1 of 19	NP_064592.3	Q5T890-1
	ERCC6L2	NM_001375291.1		c.-33A>G		5_prime_UTR	Exon 1 of 19	NP_001362220.1
	ERCC6L2	NM_001375292.1		c.-33A>G		5_prime_UTR	Exon 1 of 19	NP_001362221.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ERCC6L2	ENST00000653738.2	MANE Select	c.-33A>G		5_prime_UTR	Exon 1 of 19	ENSP00000499221.2	Q5T890-1
	ERCC6L2	ENST00000288985.13	TSL:1	c.-33A>G		5_prime_UTR	Exon 1 of 14	ENSP00000288985.8	A0A5F9UKL4
	ERCC6L2-AS1	ENST00000321517.4	TSL:1	n.5T>C		non_coding_transcript_exon	Exon 1 of 3

Frequencies

GnomAD3 genomes AF: 0.263 AC: 39914 AN: 152046 Hom.: 5849 Cov.: 33

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.307

Gnomad ASJ AF: 0.374

Gnomad EAS AF: 0.371

Gnomad SAS AF: 0.273

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.313

Gnomad OTH AF: 0.276

GnomAD2 exomes AF: 0.301 AC: 54955 AN: 182664 AF XY: 0.301

Gnomad AFR exome AF: 0.118

Gnomad AMR exome AF: 0.328

Gnomad ASJ exome AF: 0.385

Gnomad EAS exome AF: 0.382

Gnomad FIN exome AF: 0.264

Gnomad NFE exome AF: 0.307

Gnomad OTH exome AF: 0.305

GnomAD4 exome AF: 0.307 AC: 435022 AN: 1418030 Hom.: 67642 Cov.: 33 AF XY: 0.307 AC XY: 215035 AN XY: 701538

African (AFR) AF: 0.119 AC: 3857 AN: 32306

American (AMR) AF: 0.322 AC: 12667 AN: 39392

Ashkenazi Jewish (ASJ) AF: 0.385 AC: 9754 AN: 25324

East Asian (EAS) AF: 0.338 AC: 12432 AN: 36808

South Asian (SAS) AF: 0.272 AC: 22015 AN: 80848

European-Finnish (FIN) AF: 0.266 AC: 12874 AN: 48440

Middle Eastern (MID) AF: 0.255 AC: 1456 AN: 5714

European-Non Finnish (NFE) AF: 0.314 AC: 342571 AN: 1090512

Other (OTH) AF: 0.296 AC: 17396 AN: 58686

GnomAD4 genome AF: 0.262 AC: 39916 AN: 152164 Hom.: 5846 Cov.: 33 AF XY: 0.265 AC XY: 19702 AN XY: 74362

African (AFR) AF: 0.130 AC: 5412 AN: 41532

American (AMR) AF: 0.307 AC: 4691 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.374 AC: 1297 AN: 3470

East Asian (EAS) AF: 0.370 AC: 1913 AN: 5172

South Asian (SAS) AF: 0.274 AC: 1319 AN: 4820

European-Finnish (FIN) AF: 0.277 AC: 2930 AN: 10594

Middle Eastern (MID) AF: 0.279 AC: 81 AN: 290

European-Non Finnish (NFE) AF: 0.313 AC: 21302 AN: 67976

Other (OTH) AF: 0.273 AC: 577 AN: 2110

Alfa AF: 0.298 Hom.: 5428

Bravo AF: 0.258

TwinsUK AF: 0.314 AC: 1165

ALSPAC AF: 0.321 AC: 1237

ESP6500AA AF: 0.131 AC: 561

ESP6500EA AF: 0.298 AC: 2502

ExAC AF: 0.244 AC: 28272

Asia WGS AF: 0.273 AC: 946 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.53	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	9.8
DANN	Benign	0.43
Eigen	Benign	-1.6
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.00091	N
LIST_S2	Uncertain	0.90	D
MetaRNN	Benign	0.00090	T
MetaSVM	Benign	-1.1	T
PhyloP100		-0.060
PROVEAN	Benign	0.31	N
REVEL	Benign	0.23
Sift	Benign	1.0	T
Sift4G	Pathogenic	0.0	D
Vest4		0.021
ClinPred		0.0047	T
GERP RS		-3.7
PromoterAI		0.23	Neutral
gMVP		0.20
Mutation Taster		=188/12	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: rs690528; hg19: chr9-98638288; COSMIC: COSV56628012; COSMIC: COSV56628012;