Genetic Variant CHRAC1:p.Val4Ala (chr8-140511510-T-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017444.6(CHRAC1):c.11T>C(p.Val4Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

CHRAC1
NM_017444.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.0410

Publications

0 publications found

Variant links:

Genes affected

CHRAC1 (HGNC:13544): (chromatin accessibility complex subunit 1) CHRAC1 is a histone-fold protein that interacts with other histone-fold proteins to bind DNA in a sequence-independent manner. These histone-fold protein dimers combine within larger enzymatic complexes for DNA transcription, replication, and packaging.[supplied by OMIM, Apr 2004]

CHRAC1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.033998042).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017444.6. 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
	CHRAC1	NM_017444.6	MANE Select	c.11T>C	p.Val4Ala	missense	Exon 1 of 3	NP_059140.1	Q9NRG0
	CHRAC1	NR_023360.3		n.189T>C		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
CHRAC1	ENST00000220913.10	TSL:1 MANE Select	c.11T>C	p.Val4Ala	missense	Exon 1 of 3	ENSP00000220913.5	Q9NRG0
CHRAC1	ENST00000519533.1	TSL:1	c.11T>C	p.Val4Ala	missense	Exon 1 of 2	ENSP00000428697.1	E5RGS9
CHRAC1	ENST00000970390.1		c.11T>C	p.Val4Ala	missense	Exon 1 of 3	ENSP00000640449.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1191066

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

578428

African (AFR)

AF:

0.00

AC:

AN:

23856

American (AMR)

AF:

0.00

AC:

AN:

11652

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

16232

East Asian (EAS)

AF:

0.00

AC:

AN:

27338

South Asian (SAS)

AF:

0.00

AC:

AN:

47100

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42718

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4772

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

969988

Other (OTH)

AF:

0.00

AC:

AN:

47410

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.087

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.69

CADD

Benign

6.9

(source)

DANN

Benign

0.61

DEOGEN2

Benign

0.012

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.063

LIST_S2

Benign

0.35

M_CAP

Uncertain

0.11

MetaRNN

Benign

0.034

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.20

PhyloP100

-0.041

PrimateAI

Uncertain

0.73

PROVEAN

Benign

0.50

REVEL

Benign

0.017

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.067

MutPred

0.12

Loss of stability (P = 0.0765)

MVP

0.31

MPC

0.021

ClinPred

0.053

GERP RS

-2.8

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.024

gMVP

0.12

Mutation Taster

=97/3

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over