11-64357468-T-G

Variant names:

• chr11-64357468-T-G
• rs600377
• ENST00000359902.2:c.2119T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000359902.2(CCDC88B):​c.2119T>G​(p.Trp707Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.388 in 715,440 control chromosomes in the GnomAD database, including 58,498 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/16 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.33 (10201 hom., cov: 33)
  • Exomes 𝑓: 0.40 (48297 hom.)
• Consequence: CCDC88B ENST00000359902.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.228
• Publications: 26 publications found

Genes affected

CCDC88B (HGNC:26757): (coiled-coil domain containing 88B) This gene encodes a member of the hook-related protein family. Members of this family are characterized by an N-terminal potential microtubule binding domain, a central coiled-coiled and a C-terminal Hook-related domain. The encoded protein may be involved in linking organelles to microtubules. [provided by RefSeq, Oct 2009]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=7.85619E-4).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.438 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000359902.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88B	NM_032251.6	MANE Select	c.*374T>G		3_prime_UTR	Exon 27 of 27	NP_115627.6

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CCDC88B	ENST00000359902.2	TSL:1	c.2119T>G	p.Trp707Gly	missense	Exon 14 of 14	ENSP00000352974.2
	CCDC88B	ENST00000356786.10	TSL:1 MANE Select	c.*374T>G		3_prime_UTR	Exon 27 of 27	ENSP00000349238.5
	CCDC88B	ENST00000301897.5	TSL:1	c.*374T>G		3_prime_UTR	Exon 4 of 4	ENSP00000301897.4

Frequencies

GnomAD3 genomes AF: 0.329 AC: 49965 AN: 152068 Hom.: 10203 Cov.: 33

Gnomad AFR AF: 0.0876

Gnomad AMI AF: 0.384

Gnomad AMR AF: 0.377

Gnomad ASJ AF: 0.420

Gnomad EAS AF: 0.203

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.255

Gnomad NFE AF: 0.443

Gnomad OTH AF: 0.315

GnomAD2 exomes AF: 0.388 AC: 57254 AN: 147438 AF XY: 0.389

Gnomad AFR exome AF: 0.0777

Gnomad AMR exome AF: 0.394

Gnomad ASJ exome AF: 0.414

Gnomad EAS exome AF: 0.193

Gnomad FIN exome AF: 0.480

Gnomad NFE exome AF: 0.436

Gnomad OTH exome AF: 0.371

GnomAD4 exome AF: 0.404 AC: 227523 AN: 563252 Hom.: 48297 Cov.: 0 AF XY: 0.404 AC XY: 122797 AN XY: 303674

African (AFR) AF: 0.0897 AC: 1412 AN: 15750

American (AMR) AF: 0.396 AC: 13706 AN: 34646

Ashkenazi Jewish (ASJ) AF: 0.411 AC: 8196 AN: 19920

East Asian (EAS) AF: 0.214 AC: 6857 AN: 32082

South Asian (SAS) AF: 0.387 AC: 24296 AN: 62726

European-Finnish (FIN) AF: 0.478 AC: 22757 AN: 47618

Middle Eastern (MID) AF: 0.228 AC: 926 AN: 4066

European-Non Finnish (NFE) AF: 0.437 AC: 138137 AN: 315836

Other (OTH) AF: 0.367 AC: 11236 AN: 30608

GnomAD4 genome AF: 0.328 AC: 49970 AN: 152188 Hom.: 10201 Cov.: 33 AF XY: 0.332 AC XY: 24694 AN XY: 74384

African (AFR) AF: 0.0875 AC: 3637 AN: 41554

American (AMR) AF: 0.377 AC: 5765 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.420 AC: 1457 AN: 3466

East Asian (EAS) AF: 0.203 AC: 1049 AN: 5172

South Asian (SAS) AF: 0.398 AC: 1922 AN: 4828

European-Finnish (FIN) AF: 0.471 AC: 4986 AN: 10594

Middle Eastern (MID) AF: 0.245 AC: 72 AN: 294

European-Non Finnish (NFE) AF: 0.443 AC: 30076 AN: 67966

Other (OTH) AF: 0.310 AC: 657 AN: 2116

Alfa AF: 0.388 Hom.: 12125

Bravo AF: 0.307

TwinsUK AF: 0.454 AC: 1682

ALSPAC AF: 0.448 AC: 1727

ExAC AF: 0.285 AC: 6526

Asia WGS AF: 0.313 AC: 1087 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	5.4
DANN	Benign	0.83
Eigen	Benign	-0.030
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.43	N
LIST_S2	Benign	0.26	T
MetaRNN	Benign	0.00079	T
MetaSVM	Benign	-0.95	T
PhyloP100		-0.23
PROVEAN	Benign	1.1	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Vest4		0.13
ClinPred		0.022	T
GERP RS		2.9
Mutation Taster		=97/3	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: rs600377; hg19: chr11-64124940; COSMIC: COSV53700500; COSMIC: COSV53700500;