NM_000078.3:c.930+24T>G

Variant names:

• chr16-56973534-T-G
• rs11076176
• NM_000078.3:c.930+24T>G

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.930+24T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.191 in 1,612,826 control chromosomes in the GnomAD database, including 32,944 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.25 (5978 hom., cov: 32)
  • Exomes 𝑓: 0.18 (26966 hom.)
• Consequence: CETP NM_000078.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0470
• Publications: 32 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=-0.85).
• BP6: Variant 16-56973534-T-G is Benign according to our data. Variant chr16-56973534-T-G is described in ClinVar as Benign. ClinVar VariationId is 1267902.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.415 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CETP	NM_000078.3	c.930+24T>G		intron_variant	Intron 9 of 15	ENST00000200676.8	NP_000069.2
CETP	NM_001286085.2	c.750+1451T>G		intron_variant	Intron 8 of 14		NP_001273014.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CETP	ENST00000200676.8	c.930+24T>G		intron_variant	Intron 9 of 15	1	NM_000078.3	ENSP00000200676.3
CETP	ENST00000379780.6	c.750+1451T>G		intron_variant	Intron 8 of 14	1		ENSP00000369106.2
CETP	ENST00000566128.1	c.735+24T>G		intron_variant	Intron 9 of 15	5		ENSP00000456276.1
CETP	ENST00000569082.1	n.*166T>G		downstream_gene_variant		5

Frequencies

GnomAD3 genomes AF: 0.255 AC: 38692 AN: 151894 Hom.: 5961 Cov.: 32

Gnomad AFR AF: 0.420

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.266

Gnomad SAS AF: 0.214

Gnomad FIN AF: 0.147

Gnomad MID AF: 0.213

Gnomad NFE AF: 0.170

Gnomad OTH AF: 0.254

GnomAD2 exomes AF: 0.221 AC: 55240 AN: 249762 AF XY: 0.214

Gnomad AFR exome AF: 0.424

Gnomad AMR exome AF: 0.329

Gnomad ASJ exome AF: 0.152

Gnomad EAS exome AF: 0.279

Gnomad FIN exome AF: 0.156

Gnomad NFE exome AF: 0.169

Gnomad OTH exome AF: 0.189

GnomAD4 exome AF: 0.184 AC: 268841 AN: 1460812 Hom.: 26966 Cov.: 34 AF XY: 0.184 AC XY: 133435 AN XY: 726698

African (AFR) AF: 0.427 AC: 14283 AN: 33466

American (AMR) AF: 0.325 AC: 14514 AN: 44604

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 4015 AN: 26118

East Asian (EAS) AF: 0.237 AC: 9419 AN: 39680

South Asian (SAS) AF: 0.220 AC: 18980 AN: 86208

European-Finnish (FIN) AF: 0.154 AC: 8204 AN: 53204

Middle Eastern (MID) AF: 0.192 AC: 1103 AN: 5740

European-Non Finnish (NFE) AF: 0.168 AC: 186420 AN: 1111438

Other (OTH) AF: 0.197 AC: 11903 AN: 60354

GnomAD4 genome AF: 0.255 AC: 38752 AN: 152014 Hom.: 5978 Cov.: 32 AF XY: 0.255 AC XY: 18919 AN XY: 74288

African (AFR) AF: 0.420 AC: 17395 AN: 41410

American (AMR) AF: 0.302 AC: 4607 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 539 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1376 AN: 5174

South Asian (SAS) AF: 0.214 AC: 1033 AN: 4822

European-Finnish (FIN) AF: 0.147 AC: 1559 AN: 10570

Middle Eastern (MID) AF: 0.218 AC: 64 AN: 294

European-Non Finnish (NFE) AF: 0.170 AC: 11542 AN: 67978

Other (OTH) AF: 0.253 AC: 535 AN: 2114

Alfa AF: 0.138 Hom.: 429

Bravo AF: 0.276

Asia WGS AF: 0.234 AC: 813 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	-0.85
CADD	Benign	2.3
DANN	Benign	0.69
PhyloP100		-0.047
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: rs11076176; hg19: chr16-57007446; COSMIC: COSV52361776; COSMIC: COSV52361776;