18-35468653-G-A

Variant names:

• chr18-35468653-G-A
• rs34130630
• NM_194281.4:c.537C>T

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BS1 BS2

The NM_194281.4(INO80C):​c.537C>T​(p.Thr179Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00244 in 1,614,010 control chromosomes in the GnomAD database, including 90 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.012 (46 hom., cov: 32)
  • Exomes 𝑓: 0.0014 (44 hom.)
• Consequence: INO80C NM_194281.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -1.53
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 18-35468653-G-A is Benign according to our data. Variant chr18-35468653-G-A is described in ClinVar as Benign. ClinVar VariationId is 786660.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.53 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0121 (1839/152158) while in subpopulation AFR AF = 0.0416 (1724/41492). AF 95% confidence interval is 0.0399. There are 46 homozygotes in GnomAd4. There are 846 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_194281.4. 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
	INO80C	NM_194281.4	MANE Select	c.537C>T	p.Thr179Thr	synonymous	Exon 5 of 5	NP_919257.2
	INO80C	NM_001098817.2		c.645C>T	p.Thr215Thr	synonymous	Exon 7 of 7	NP_001092287.1	Q6PI98-4
	INO80C	NM_001308064.2		c.372C>T	p.Thr124Thr	synonymous	Exon 5 of 5	NP_001294993.1	K7EIY8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INO80C	ENST00000334598.12	TSL:1 MANE Select	c.537C>T	p.Thr179Thr	synonymous	Exon 5 of 5	ENSP00000334473.6	Q6PI98-1
	ENSG00000267140	ENST00000589258.1	TSL:3	c.157-21698C>T		intron	N/A	ENSP00000467041.1	K7ENP7
	INO80C	ENST00000441607.6	TSL:2	c.645C>T	p.Thr215Thr	synonymous	Exon 7 of 7	ENSP00000391457.1	Q6PI98-4

Frequencies

GnomAD3 genomes AF: 0.0120 AC: 1825 AN: 152040 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00439

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.000382

Gnomad OTH AF: 0.00911

GnomAD2 exomes AF: 0.00339 AC: 851 AN: 251398 AF XY: 0.00250

Gnomad AFR exome AF: 0.0453

Gnomad AMR exome AF: 0.00220

Gnomad ASJ exome AF: 0.0000992

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000176

Gnomad OTH exome AF: 0.00244

GnomAD4 exome AF: 0.00143 AC: 2097 AN: 1461852 Hom.: 44 Cov.: 34 AF XY: 0.00128 AC XY: 931 AN XY: 727228

African (AFR) AF: 0.0459 AC: 1537 AN: 33480

American (AMR) AF: 0.00250 AC: 112 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000927 AC: 8 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.00260 AC: 15 AN: 5768

European-Non Finnish (NFE) AF: 0.000205 AC: 228 AN: 1111970

Other (OTH) AF: 0.00321 AC: 194 AN: 60396

GnomAD4 genome AF: 0.0121 AC: 1839 AN: 152158 Hom.: 46 Cov.: 32 AF XY: 0.0114 AC XY: 846 AN XY: 74410

African (AFR) AF: 0.0416 AC: 1724 AN: 41492

American (AMR) AF: 0.00438 AC: 67 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10594

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 292

European-Non Finnish (NFE) AF: 0.000382 AC: 26 AN: 68008

Other (OTH) AF: 0.00901 AC: 19 AN: 2108

Alfa AF: 0.00604 Hom.: 11

Bravo AF: 0.0137

Asia WGS AF: 0.00347 AC: 12 AN: 3476

EpiCase AF: 0.000109

EpiControl AF: 0.000296

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	-0.66
CADD	Benign	3.2
DANN	Benign	0.82
PhyloP100		-1.5
Mutation Taster		=98/2	polymorphism

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: rs34130630; hg19: chr18-33048617;