6-4943770-TAAAAAAAA-TAAAAAAAAA

Variant names:

• chr6-4943770-T-TA
• rs34649909
• NM_004824.4:c.1332+31dupA

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_004824.4(CDYL):​c.1332+31dupA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.52 (21342 hom., cov: 0)
  • Exomes 𝑓: 0.39 (5203 hom.)
  • Failed GnomAD Quality Control
• Consequence: CDYL NM_004824.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.378
• Publications: 0 publications found

Genes affected

CDYL (HGNC:1811): (chromodomain Y like) Chromodomain Y is a primate-specific Y-chromosomal gene family expressed exclusively in the testis and implicated in infertility. Although the Y-linked genes are testis-specific, this autosomal gene is ubiquitously expressed. The Y-linked genes arose by retrotransposition of an mRNA from this gene, followed by amplification of the retroposed gene. Proteins encoded by this gene superfamily possess a chromodomain, a motif implicated in chromatin binding and gene suppression, and a catalytic domain believed to be involved in histone acetylation. Multiple proteins are encoded by transcript variants of this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 6-4943770-T-TA is Benign according to our data. Variant chr6-4943770-T-TA is described in ClinVar as Benign. ClinVar VariationId is 402525.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.68 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDYL	NM_004824.4	c.1332+31dupA		intron_variant	Intron 5 of 6	ENST00000397588.8	NP_004815.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDYL	ENST00000397588.8	c.1332+31dupA		intron_variant	Intron 5 of 6	1	NM_004824.4	ENSP00000380718.3

Frequencies

GnomAD3 genomes AF: 0.522 AC: 75328 AN: 144184 Hom.: 21369 Cov.: 0

Gnomad AFR AF: 0.270

Gnomad AMI AF: 0.453

Gnomad AMR AF: 0.594

Gnomad ASJ AF: 0.640

Gnomad EAS AF: 0.699

Gnomad SAS AF: 0.670

Gnomad FIN AF: 0.534

Gnomad MID AF: 0.714

Gnomad NFE AF: 0.622

Gnomad OTH AF: 0.591

GnomAD2 exomes AF: 0.362 AC: 51313 AN: 141918 AF XY: 0.365

Gnomad AFR exome AF: 0.210

Gnomad AMR exome AF: 0.379

Gnomad ASJ exome AF: 0.358

Gnomad EAS exome AF: 0.404

Gnomad FIN exome AF: 0.347

Gnomad NFE exome AF: 0.374

Gnomad OTH exome AF: 0.369

GnomAD4 exome Data not reliable, filtered out with message: InbreedingCoeff AF: 0.387 AC: 392208 AN: 1012966 Hom.: 5203 Cov.: 17 AF XY: 0.387 AC XY: 196450 AN XY: 507000

African (AFR) AF: 0.219 AC: 5311 AN: 24200

American (AMR) AF: 0.375 AC: 9599 AN: 25620

Ashkenazi Jewish (ASJ) AF: 0.383 AC: 6941 AN: 18140

East Asian (EAS) AF: 0.423 AC: 14337 AN: 33914

South Asian (SAS) AF: 0.382 AC: 22496 AN: 58944

European-Finnish (FIN) AF: 0.349 AC: 14137 AN: 40516

Middle Eastern (MID) AF: 0.405 AC: 1175 AN: 2900

European-Non Finnish (NFE) AF: 0.394 AC: 301574 AN: 765288

Other (OTH) AF: 0.383 AC: 16638 AN: 43444

GnomAD4 genome AF: 0.522 AC: 75299 AN: 144216 Hom.: 21342 Cov.: 0 AF XY: 0.521 AC XY: 36298 AN XY: 69678

African (AFR) AF: 0.270 AC: 10547 AN: 39044

American (AMR) AF: 0.594 AC: 8650 AN: 14572

Ashkenazi Jewish (ASJ) AF: 0.640 AC: 2189 AN: 3418

East Asian (EAS) AF: 0.699 AC: 3449 AN: 4932

South Asian (SAS) AF: 0.669 AC: 3022 AN: 4516

European-Finnish (FIN) AF: 0.534 AC: 4390 AN: 8220

Middle Eastern (MID) AF: 0.714 AC: 200 AN: 280

European-Non Finnish (NFE) AF: 0.622 AC: 41269 AN: 66346

Other (OTH) AF: 0.591 AC: 1175 AN: 1988

Alfa AF: 0.00 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Mar 29, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.38
Mutation Taster		=100/0	polymorphism (auto)

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: rs34649909; hg19: chr6-4944004;