chr8-140511537-A-G

Position:

• chr8-140511537-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_017444.6(CHRAC1):​c.38A>G​(p.Glu13Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000159 in 1,261,706 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000016 (0 hom.)
• Consequence: CHRAC1 NM_017444.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 2.23

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25371593).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CHRAC1	NM_017444.6	c.38A>G	p.Glu13Gly	missense_variant	1/3	ENST00000220913.10	NP_059140.1
CHRAC1	NR_023360.3	n.216A>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CHRAC1	ENST00000220913.10	c.38A>G	p.Glu13Gly	missense_variant	1/3	1	NM_017444.6	ENSP00000220913.5
CHRAC1	ENST00000519533.1	c.38A>G	p.Glu13Gly	missense_variant	1/2	1		ENSP00000428697.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000159 AC: 2 AN: 1261706 Hom.: 0 Cov.: 30 AF XY: 0.00000161 AC XY: 1 AN XY: 621366

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000502

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.0000198

GnomAD4 genome Cov.: 32

Bravo AF: 0.0000113

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 23, 2023

The c.38A>G (p.E13G) alteration is located in exon 1 (coding exon 1) of the CHRAC1 gene. This alteration results from a A to G substitution at nucleotide position 38, causing the glutamic acid (E) at amino acid position 13 to be replaced by a glycine (G). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.49
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.030	T;.
Eigen	Benign	-0.23
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.73	D
LIST_S2	Benign	0.58	T;T
M_CAP	Pathogenic	0.56	D
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.90	L;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Benign	-1.5	N;N
REVEL	Benign	0.033
Sift	Benign	0.13	T;T
Sift4G	Benign	0.13	T;T
Polyphen		0.15	B;.
Vest4		0.14
MutPred		0.24		Gain of MoRF binding (P = 0.03);Gain of MoRF binding (P = 0.03);
MVP		0.32
MPC		0.021
ClinPred		0.23	T
GERP RS		3.1
Varity_R		0.12
gMVP		0.12

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs1218692828; hg19: chr8-141521636;