chr22-17538986-C-T

Variant names:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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. GnomAdExome4 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 GnomAdExome4. There are 9144 alleles in the male GnomAdExome4 subpopulation. Median coverage is 31. This position passed quality control check.
• 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

GnomAD2 exomes AF: 0.00751 AC: 1865 AN: 248214 AF XY: 0.00769

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 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

African (AFR) AF: 0.00329 AC: 110 AN: 33422

American (AMR) AF: 0.00501 AC: 223 AN: 44510

Ashkenazi Jewish (ASJ) AF: 0.000115 AC: 3 AN: 26086

East Asian (EAS) AF: 0.00 AC: 0 AN: 39666

South Asian (SAS) AF: 0.00469 AC: 403 AN: 85998

European-Finnish (FIN) AF: 0.00201 AC: 107 AN: 53318

Middle Eastern (MID) AF: 0.00174 AC: 10 AN: 5754

European-Non Finnish (NFE) AF: 0.0156 AC: 17373 AN: 1110838

Other (OTH) AF: 0.0105 AC: 632 AN: 60292

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

African (AFR) AF: 0.00479 AC: 199 AN: 41522

American (AMR) AF: 0.00694 AC: 106 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5180

South Asian (SAS) AF: 0.00352 AC: 17 AN: 4824

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10586

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0129 AC: 876 AN: 68012

Other (OTH) AF: 0.00568 AC: 12 AN: 2114

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
PhyloP100		0.39
Mutation Taster		=100/0	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: rs35746048; hg19: chr22-18018675; COSMIC: COSV107288019;