22-17538986-C-T

Variant names:

• chr22-17538986-C-T
• rs35746048
• NM_001290047.2:c.1369-7C>T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001290047.2(CECR2):​c.1369-7C>T variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0125 in 1,612,074 control chromosomes in the GnomAD database, including 187 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0081 (5 hom., cov: 33)
  • Exomes 𝑓: 0.013 (182 hom.)
• Consequence: CECR2 NM_001290047.2 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.387

Genes affected

CECR2 (HGNC:1840): (CECR2 histone acetyl-lysine reader) This gene encodes a bromodomain-containing protein that is involved in chromatin remodeling, and may additionally play a role in DNA damage response. The encoded protein functions as part of an ATP-dependent complex that is involved in neurulation. This gene is a candidate gene for Cat Eye Syndrome. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2014]

ENSG00000286195 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 22-17538986-C-T is Benign according to our data. Variant chr22-17538986-C-T is described in ClinVar as [Benign]. Clinvar id is 790383.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4_exome allele frequency = 0.0129 (18861/1459884) while in subpopulation NFE AF= 0.0156 (17373/1110838). AF 95% confidence interval is 0.0154. There are 182 homozygotes in gnomad4_exome. There are 9144 alleles in male gnomad4_exome subpopulation. Median coverage is 31. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1226 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CECR2	NM_001290047.2	c.1369-7C>T		splice_region_variant, intron_variant	Intron 12 of 18	ENST00000262608.13	NP_001276976.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CECR2	ENST00000262608.13	c.1369-7C>T		splice_region_variant, intron_variant	Intron 12 of 18	1	NM_001290047.2	ENSP00000262608.11

Frequencies

GnomAD3 genomes AF: 0.00807 AC: 1227 AN: 152072 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.00481

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00695

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00352

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0129

Gnomad OTH AF: 0.00574

GnomAD3 exomes AF: 0.00751 AC: 1865 AN: 248214 Hom.: 18 AF XY: 0.00769 AC XY: 1036 AN XY: 134648

Gnomad AFR exome AF: 0.00439

Gnomad AMR exome AF: 0.00551

Gnomad ASJ exome AF: 0.000100

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00480

Gnomad FIN exome AF: 0.00182

Gnomad NFE exome AF: 0.0122

Gnomad OTH exome AF: 0.00813

GnomAD4 exome AF: 0.0129 AC: 18861 AN: 1459884 Hom.: 182 Cov.: 31 AF XY: 0.0126 AC XY: 9144 AN XY: 726196

Gnomad4 AFR exome AF: 0.00329

Gnomad4 AMR exome AF: 0.00501

Gnomad4 ASJ exome AF: 0.000115

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00469

Gnomad4 FIN exome AF: 0.00201

Gnomad4 NFE exome AF: 0.0156

Gnomad4 OTH exome AF: 0.0105

GnomAD4 genome AF: 0.00806 AC: 1226 AN: 152190 Hom.: 5 Cov.: 33 AF XY: 0.00717 AC XY: 533 AN XY: 74386

Gnomad4 AFR AF: 0.00479

Gnomad4 AMR AF: 0.00694

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00352

Gnomad4 FIN AF: 0.00151

Gnomad4 NFE AF: 0.0129

Gnomad4 OTH AF: 0.00568

Alfa AF: 0.00974 Hom.: 7

Bravo AF: 0.00843

Asia WGS AF: 0.00404 AC: 14 AN: 3478

EpiCase AF: 0.0124

EpiControl AF: 0.0127

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 05, 2018

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.2
DANN	Benign	0.19

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

Publications

LitVar

Other links and lift over

dbSNP: rs35746048; hg19: chr22-18018675;