18-35478355-A-G

Variant names:

• chr18-35478355-A-G
• rs11081906
• NM_194281.4:c.380-6T>C

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_194281.4(INO80C):​c.380-6T>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0509 in 430,740 control chromosomes in the GnomAD database, including 681 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.034 (508 hom., cov: 31)
  • Exomes 𝑓: 0.059 (173 hom.)
• Consequence: INO80C NM_194281.4 splice_region, intron
• Scores: Splicing: ADA: 0.000007674
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.977

Genes affected

INO80C (HGNC:26994): (INO80 complex subunit C) Predicted to be involved in chromatin remodeling. Part of Ino80 complex and MLL1 complex. [provided by Alliance of Genome Resources, Apr 2022]

ENSG00000267140 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 18-35478355-A-G is Benign according to our data. Variant chr18-35478355-A-G is described in ClinVar as [Benign]. Clinvar id is 780171.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.399 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
INO80C	NM_194281.4	c.380-6T>C		splice_region_variant, intron_variant	Intron 3 of 4	ENST00000334598.12	NP_919257.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
INO80C	ENST00000334598.12	c.380-6T>C		splice_region_variant, intron_variant	Intron 3 of 4	1	NM_194281.4	ENSP00000334473.6
ENSG00000267140	ENST00000589258.1	c.156+19364T>C		intron_variant	Intron 1 of 2	3		ENSP00000467041.1

Frequencies

GnomAD3 genomes AF: 0.0338 AC: 4747 AN: 140350 Hom.: 509 Cov.: 31

Gnomad AFR AF: 0.0405

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0318

Gnomad ASJ AF: 0.0169

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.0920

Gnomad FIN AF: 0.00415

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00231

Gnomad OTH AF: 0.0325

GnomAD4 exome AF: 0.0592 AC: 17199 AN: 290372 Hom.: 173 Cov.: 0 AF XY: 0.0635 AC XY: 9033 AN XY: 142284

Gnomad4 AFR exome AF: 0.112

Gnomad4 AMR exome AF: 0.129

Gnomad4 ASJ exome AF: 0.0814

Gnomad4 EAS exome AF: 0.457

Gnomad4 SAS exome AF: 0.200

Gnomad4 FIN exome AF: 0.0181

Gnomad4 NFE exome AF: 0.00428

Gnomad4 OTH exome AF: 0.114

GnomAD4 genome AF: 0.0338 AC: 4742 AN: 140368 Hom.: 508 Cov.: 31 AF XY: 0.0367 AC XY: 2503 AN XY: 68210

Gnomad4 AFR AF: 0.0404

Gnomad4 AMR AF: 0.0318

Gnomad4 ASJ AF: 0.0169

Gnomad4 EAS AF: 0.414

Gnomad4 SAS AF: 0.0924

Gnomad4 FIN AF: 0.00415

Gnomad4 NFE AF: 0.00231

Gnomad4 OTH AF: 0.0327

Alfa AF: 0.0103 Hom.: 19

Bravo AF: 0.0327

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	0.25
DANN	Benign	0.51

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.0000077
dbscSNV1_RF	Benign	0.0
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

Publications

LitVar

Other links and lift over

dbSNP: rs11081906; hg19: chr18-33058319;