16-56962246-T-C

Variant names:

• chr16-56962246-T-C
• rs3816117
• NM_000078.3:c.118+149T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_000078.3(CETP):​c.118+149T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.513 in 768,876 control chromosomes in the GnomAD database, including 102,113 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.52 (20861 hom., cov: 31)
  • Exomes 𝑓: 0.51 (81252 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -2.13
• Publications: 35 publications found

Genes affected

CETP (HGNC:1869): (cholesteryl ester transfer protein) The protein encoded by this gene is found in plasma, where it is involved in the transfer of cholesteryl ester from high density lipoprotein (HDL) to other lipoproteins. Defects in this gene are a cause of hyperalphalipoproteinemia 1 (HALP1). Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2013]

CETP Gene-Disease associations (from GenCC):

• cholesterol-ester transfer protein deficiency

  Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BP6: Variant 16-56962246-T-C is Benign according to our data. Variant chr16-56962246-T-C is described in ClinVar as [Benign]. Clinvar id is 1267499.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.118+149T>C		intron_variant	Intron 1 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.118+149T>C		intron_variant	Intron 1 of 14		NP_001273014.1
CETP	XM_006721124.4	c.118+149T>C		intron_variant	Intron 1 of 8		XP_006721187.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.118+149T>C		intron_variant	Intron 1 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.118+149T>C		intron_variant	Intron 1 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.-128T>C		5_prime_UTR_variant	Exon 1 of 16	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.116+149T>C		intron_variant	Intron 1 of 8	5

Frequencies

GnomAD3 genomes AF: 0.522 AC: 79155 AN: 151654 Hom.: 20829 Cov.: 31

Gnomad AFR AF: 0.570

Gnomad AMI AF: 0.652

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.532

Gnomad EAS AF: 0.495

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.510

Gnomad MID AF: 0.519

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.502

GnomAD4 exome AF: 0.510 AC: 315024 AN: 617104 Hom.: 81252 Cov.: 7 AF XY: 0.515 AC XY: 173009 AN XY: 335656

African (AFR) AF: 0.566 AC: 10047 AN: 17766

American (AMR) AF: 0.536 AC: 21789 AN: 40672

Ashkenazi Jewish (ASJ) AF: 0.534 AC: 10947 AN: 20514

East Asian (EAS) AF: 0.523 AC: 18588 AN: 35530

South Asian (SAS) AF: 0.608 AC: 41336 AN: 67982

European-Finnish (FIN) AF: 0.501 AC: 18939 AN: 37776

Middle Eastern (MID) AF: 0.506 AC: 2097 AN: 4144

European-Non Finnish (NFE) AF: 0.485 AC: 174520 AN: 359718

Other (OTH) AF: 0.508 AC: 16761 AN: 33002

GnomAD4 genome AF: 0.522 AC: 79231 AN: 151772 Hom.: 20861 Cov.: 31 AF XY: 0.526 AC XY: 38979 AN XY: 74154

African (AFR) AF: 0.571 AC: 23643 AN: 41414

American (AMR) AF: 0.507 AC: 7735 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.532 AC: 1844 AN: 3468

East Asian (EAS) AF: 0.495 AC: 2544 AN: 5140

South Asian (SAS) AF: 0.610 AC: 2936 AN: 4814

European-Finnish (FIN) AF: 0.510 AC: 5356 AN: 10502

Middle Eastern (MID) AF: 0.500 AC: 146 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33380 AN: 67868

Other (OTH) AF: 0.501 AC: 1052 AN: 2100

Alfa AF: 0.518 Hom.: 15122

Bravo AF: 0.522

Asia WGS AF: 0.542 AC: 1887 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aug 30, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.37
DANN	Benign	0.60
PhyloP100		-2.1
PromoterAI		0.033	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		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: rs3816117; hg19: chr16-56996158; COSMIC: COSV107216197;