rs140092191

chr12-122380446-T-C

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 1P and 8B. PP2 BP4_Strong BS2

The NM_001247997.2(CLIP1):c.7A>G(p.Met3Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0011 in 1,610,882 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00097 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (5 hom.)
• Consequence: CLIP1 NM_001247997.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.21

Genes affected

CLIP1 (HGNC:10461): (CAP-Gly domain containing linker protein 1) The protein encoded by this gene links endocytic vesicles to microtubules. This gene is highly expressed in Reed-Sternberg cells of Hodgkin disease. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2011]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• PP2: Missense variant where missense usually causes diseases, CLIP1
• BP4: Computational evidence support a benign effect (MetaRNN=0.011199325).
• BS2: High AC in GnomAd at 148 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CLIP1	NM_001247997.2	c.7A>G	p.Met3Val	missense_variant	2/26	ENST00000620786.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CLIP1	ENST00000620786.5	c.7A>G	p.Met3Val	missense_variant	2/26	5	NM_001247997.2	A1

Frequencies

GnomAD3 genomes AF: 0.000972 AC: 148 AN: 152204 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00275

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00123

Gnomad OTH AF: 0.00382

GnomAD3 exomes AF: 0.000808 AC: 201 AN: 248842 Hom.: 2 AF XY: 0.000854 AC XY: 115 AN XY: 134594

Gnomad AFR exome AF: 0.000124

Gnomad AMR exome AF: 0.00230

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000464

Gnomad NFE exome AF: 0.000964

Gnomad OTH exome AF: 0.00182

GnomAD4 exome AF: 0.00111 AC: 1626 AN: 1458560 Hom.: 5 Cov.: 29 AF XY: 0.00111 AC XY: 805 AN XY: 725806

Gnomad4 AFR exome AF: 0.0000901

Gnomad4 AMR exome AF: 0.00221

Gnomad4 ASJ exome AF: 0.000192

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000116

Gnomad4 FIN exome AF: 0.0000563

Gnomad4 NFE exome AF: 0.00130

Gnomad4 OTH exome AF: 0.00113

GnomAD4 genome AF: 0.000972 AC: 148 AN: 152322 Hom.: 1 Cov.: 32 AF XY: 0.000953 AC XY: 71 AN XY: 74486

Gnomad4 AFR AF: 0.000313

Gnomad4 AMR AF: 0.00275

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00123

Gnomad4 OTH AF: 0.00378

Alfa AF: 0.00107 Hom.: 0

Bravo AF: 0.000960

TwinsUK AF: 0.000270 AC: 1

ALSPAC AF: 0.00156 AC: 6

ESP6500AA AF: 0.000454 AC: 2

ESP6500EA AF: 0.00116 AC: 10

ExAC AF: 0.000576 AC: 70

EpiCase AF: 0.00121

EpiControl AF: 0.00125

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Jan 31, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.068
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.14
Cadd	Benign	8.0
Dann	Benign	0.94
Eigen	Benign	-0.42
Eigen_PC	Benign	-0.37
FATHMM_MKL	Uncertain	0.87	D
LIST_S2	Benign	0.83	T;.;T;T;T;.;T;T;T
M_CAP	Benign	0.019	T
MetaRNN	Benign	0.011	T;T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.57	T
MutationTaster	Benign	0.97	N;N;N;N
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-2.2	N;N;N;.;N;N;N;N;N
Sift	Uncertain	0.025	D;T;T;.;T;T;D;D;T
Sift4G	Benign	0.40	T;T;T;T;T;T;.;.;.
Polyphen		0.023, 0.0080, 0.013	.;B;B;B;B;B;.;.;.
Vest4		0.22
MVP		0.78
MPC		0.42
ClinPred		0.022	T
GERP RS		1.3
Varity_R		0.16
gMVP		0.41

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

Publications

LitVar

Other links and lift over

dbSNP: rs140092191; hg19: chr12-122864993;