chr16-56971389-C-T

Variant names:

• chr16-56971389-C-T
• rs1532625
• NM_000078.3:c.658+8C>T

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.658+8C>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 0.417 in 1,611,616 control chromosomes in the GnomAD database, including 144,548 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.34 (10314 hom., cov: 32)
  • Exomes 𝑓: 0.42 (134234 hom.)
• Consequence: CETP NM_000078.3 splice_region, intron
• Scores: Splicing: ADA: 0.0001526
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -0.729
• Publications: 49 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: Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 16-56971389-C-T is Benign according to our data. Variant chr16-56971389-C-T is described in ClinVar as Benign. ClinVar VariationId is 319981.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.46 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000078.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	NM_000078.3	MANE Select	c.658+8C>T		splice_region intron	N/A	NP_000069.2	P11597-1
	CETP	NM_001286085.2		c.658+8C>T		splice_region intron	N/A	NP_001273014.1	A0A0S2Z3I8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CETP	ENST00000200676.8	TSL:1 MANE Select	c.658+8C>T		splice_region intron	N/A	ENSP00000200676.3	P11597-1
	CETP	ENST00000379780.6	TSL:1	c.658+8C>T		splice_region intron	N/A	ENSP00000369106.2	P11597-2
	CETP	ENST00000858282.1		c.658+8C>T		splice_region intron	N/A	ENSP00000528341.1

Frequencies

GnomAD3 genomes AF: 0.344 AC: 52308 AN: 151928 Hom.: 10319 Cov.: 32

Gnomad AFR AF: 0.149

Gnomad AMI AF: 0.525

Gnomad AMR AF: 0.344

Gnomad ASJ AF: 0.390

Gnomad EAS AF: 0.283

Gnomad SAS AF: 0.475

Gnomad FIN AF: 0.422

Gnomad MID AF: 0.380

Gnomad NFE AF: 0.442

Gnomad OTH AF: 0.344

GnomAD2 exomes AF: 0.397 AC: 99581 AN: 250894 AF XY: 0.408

Gnomad AFR exome AF: 0.145

Gnomad AMR exome AF: 0.372

Gnomad ASJ exome AF: 0.386

Gnomad EAS exome AF: 0.291

Gnomad FIN exome AF: 0.413

Gnomad NFE exome AF: 0.434

Gnomad OTH exome AF: 0.410

GnomAD4 exome AF: 0.425 AC: 620048 AN: 1459570 Hom.: 134234 Cov.: 35 AF XY: 0.428 AC XY: 310766 AN XY: 726270

African (AFR) AF: 0.141 AC: 4729 AN: 33472

American (AMR) AF: 0.366 AC: 16387 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.387 AC: 10111 AN: 26126

East Asian (EAS) AF: 0.290 AC: 11509 AN: 39688

South Asian (SAS) AF: 0.481 AC: 41484 AN: 86226

European-Finnish (FIN) AF: 0.419 AC: 22156 AN: 52884

Middle Eastern (MID) AF: 0.391 AC: 2256 AN: 5764

European-Non Finnish (NFE) AF: 0.438 AC: 486827 AN: 1110370

Other (OTH) AF: 0.408 AC: 24589 AN: 60322

GnomAD4 genome AF: 0.344 AC: 52298 AN: 152046 Hom.: 10314 Cov.: 32 AF XY: 0.346 AC XY: 25737 AN XY: 74316

African (AFR) AF: 0.148 AC: 6159 AN: 41494

American (AMR) AF: 0.344 AC: 5256 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.390 AC: 1353 AN: 3472

East Asian (EAS) AF: 0.283 AC: 1458 AN: 5154

South Asian (SAS) AF: 0.476 AC: 2294 AN: 4822

European-Finnish (FIN) AF: 0.422 AC: 4455 AN: 10546

Middle Eastern (MID) AF: 0.371 AC: 109 AN: 294

European-Non Finnish (NFE) AF: 0.442 AC: 30020 AN: 67960

Other (OTH) AF: 0.340 AC: 717 AN: 2110

Alfa AF: 0.392 Hom.: 22552

Bravo AF: 0.327

Asia WGS AF: 0.351 AC: 1221 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	3	not provided (3)
-	-	2	Hyperalphalipoproteinemia 1 (2)
-	-	2	not specified (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.76
DANN	Benign	0.77
PhyloP100		-0.73
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00015
dbscSNV1_RF	Benign	0.0
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: rs1532625; hg19: chr16-57005301; COSMIC: COSV52363738;