1-45500031-G-T

Position:

• chr1-45500031-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000629482.3(CCDC163):​c.-422C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 519,220 control chromosomes in the GnomAD database, including 135,946 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41787 hom., cov: 31)
  • Exomes 𝑓: 0.71 (94159 hom.)
• Consequence: CCDC163 ENST00000629482.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.682

Genes affected

CCDC163 (HGNC:27003): (CCDC163 homolog) Predicted to be integral component of membrane. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-45500031-G-T is Benign according to our data. Variant chr1-45500031-G-T is described in ClinVar as [Benign]. Clinvar id is 684370.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-45500031-G-T is described in Lovd as [Benign].
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.92 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CCDC163	NM_001102601.3	c.-422C>A		5_prime_UTR_variant	1/5	ENST00000629482.3	NP_001096071.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CCDC163	ENST00000629482.3	c.-422C>A		5_prime_UTR_variant	1/5	1	NM_001102601.3	ENSP00000486197	P4
CCDC163	ENST00000625766.2	c.-422C>A		5_prime_UTR_variant, NMD_transcript_variant	1/5	1		ENSP00000486505
CCDC163	ENST00000626177.2	c.-422C>A		5_prime_UTR_variant, NMD_transcript_variant	1/6	1		ENSP00000485784
CCDC163	ENST00000628397.2	n.23C>A		non_coding_transcript_exon_variant	1/5	3

Frequencies

GnomAD3 genomes AF: 0.738 AC: 112041 AN: 151912 Hom.: 41753 Cov.: 31

Gnomad AFR AF: 0.818

Gnomad AMI AF: 0.762

Gnomad AMR AF: 0.800

Gnomad ASJ AF: 0.734

Gnomad EAS AF: 0.942

Gnomad SAS AF: 0.757

Gnomad FIN AF: 0.678

Gnomad MID AF: 0.756

Gnomad NFE AF: 0.667

Gnomad OTH AF: 0.735

GnomAD4 exome AF: 0.711 AC: 260924 AN: 367190 Hom.: 94159 Cov.: 2 AF XY: 0.710 AC XY: 137491 AN XY: 193660

Gnomad4 AFR exome AF: 0.817

Gnomad4 AMR exome AF: 0.844

Gnomad4 ASJ exome AF: 0.731

Gnomad4 EAS exome AF: 0.950

Gnomad4 SAS exome AF: 0.733

Gnomad4 FIN exome AF: 0.675

Gnomad4 NFE exome AF: 0.667

Gnomad4 OTH exome AF: 0.716

GnomAD4 genome AF: 0.738 AC: 112131 AN: 152030 Hom.: 41787 Cov.: 31 AF XY: 0.742 AC XY: 55143 AN XY: 74310

Gnomad4 AFR AF: 0.818

Gnomad4 AMR AF: 0.800

Gnomad4 ASJ AF: 0.734

Gnomad4 EAS AF: 0.942

Gnomad4 SAS AF: 0.757

Gnomad4 FIN AF: 0.678

Gnomad4 NFE AF: 0.667

Gnomad4 OTH AF: 0.737

Alfa AF: 0.569 Hom.: 1498

Bravo AF: 0.749

Asia WGS AF: 0.857 AC: 2979 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 19, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.77
CADD	Benign	13
DANN	Benign	0.72

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs3748643; hg19: chr1-45965703;