Variant 10-122850511-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152644.3(FAM24B):c.5C>T(p.Pro2Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 1,608,986 control chromosomes in the GnomAD database, including 242,110 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.54 ( 22403 hom., cov: 31)

Exomes 𝑓: 0.55 ( 219707 hom. )

Consequence

FAM24B
NM_152644.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 1.22

Variant links:

Genes affected

FAM24B (HGNC:23475): (family with sequence similarity 24 member B) Predicted to be located in extracellular region. [provided by Alliance of Genome Resources, Apr 2022]

FAM24B links:

FAM24B-CUZD1 (HGNC:):

FAM24B-CUZD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.6099548E-5).

BP6

Variant 10-122850511-G-A is Benign according to our data. Variant chr10-122850511-G-A is described in ClinVar as [Benign]. Clinvar id is 1280358.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FAM24B	NM_152644.3 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/4	ENST00000368898.8
FAM24B-CUZD1	NR_037915.1 linkuse as main transcript	n.300-4291C>T		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/4
FAM24B	NR_037911.1 linkuse as main transcript	n.300-1072C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
FAM24B	ENST00000368898.8 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/4	1	NM_152644.3	P1
FAM24B	ENST00000368896.1 linkuse as main transcript	c.5C>T	p.Pro2Leu	missense_variant	3/4	2		P1
FAM24B	ENST00000462859.5 linkuse as main transcript	n.300-1072C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes

AF:

0.541

AC:

82086

AN:

151864

Hom.:

22370

Cov.:

show subpopulations

Gnomad AFR

AF:

0.510

Gnomad AMI

AF:

0.739

Gnomad AMR

AF:

0.503

Gnomad ASJ

AF:

0.523

Gnomad EAS

AF:

0.506

Gnomad SAS

AF:

0.476

Gnomad FIN

AF:

0.646

Gnomad MID

AF:

0.478

Gnomad NFE

AF:

0.557

Gnomad OTH

AF:

0.530

GnomAD3 exomes

AF:

0.530

AC:

133068

AN:

251268

Hom.:

35760

AF XY:

0.531

AC XY:

72045

AN XY:

135784

show subpopulations

Gnomad AFR exome

AF:

0.505

Gnomad AMR exome

AF:

0.446

Gnomad ASJ exome

AF:

0.518

Gnomad EAS exome

AF:

0.514

Gnomad SAS exome

AF:

0.485

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.553

Gnomad OTH exome

AF:

0.534

GnomAD4 exome

AF:

0.547

AC:

796951

AN:

1457006

Hom.:

219707

Cov.:

AF XY:

0.545

AC XY:

395378

AN XY:

725110

show subpopulations

Gnomad4 AFR exome

AF:

0.514

Gnomad4 AMR exome

AF:

0.454

Gnomad4 ASJ exome

AF:

0.520

Gnomad4 EAS exome

AF:

0.526

Gnomad4 SAS exome

AF:

0.482

Gnomad4 FIN exome

AF:

0.636

Gnomad4 NFE exome

AF:

0.555

Gnomad4 OTH exome

AF:

0.536

GnomAD4 genome

AF:

0.541

AC:

82169

AN:

151980

Hom.:

22403

Cov.:

AF XY:

0.542

AC XY:

40301

AN XY:

74290

show subpopulations

Gnomad4 AFR

AF:

0.511

Gnomad4 AMR

AF:

0.503

Gnomad4 ASJ

AF:

0.523

Gnomad4 EAS

AF:

0.508

Gnomad4 SAS

AF:

0.475

Gnomad4 FIN

AF:

0.646

Gnomad4 NFE

AF:

0.557

Gnomad4 OTH

AF:

0.530

Alfa

AF:

0.545

Hom.:

59697

Bravo

AF:

0.528

TwinsUK

AF:

0.566

AC:

2098

ALSPAC

AF:

0.542

AC:

2088

ESP6500AA

AF:

0.520

AC:

2292

ESP6500EA

AF:

0.555

AC:

4772

ExAC

AF:

0.528

AC:

64145

Asia WGS

AF:

0.489

AC:

1699

AN:

3478

EpiCase

AF:

0.537

EpiControl

AF:

0.543

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 10, 2019	This variant is associated with the following publications: (PMID: 29083408) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.047

BayesDel_addAF

Benign

-0.76

BayesDel_noAF

Benign

-0.72

CADD

Benign

3.3

DANN

Benign

0.64

DEOGEN2

Benign

0.0032

T;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.00083

LIST_S2

Benign

0.28

.;T

MetaRNN

Benign

0.000016

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

P;P;P;P

PrimateAI

Benign

0.29

PROVEAN

Benign

5.0

N;N

REVEL

Benign

0.067

Sift

Benign

0.70

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.020

MPC

0.26

ClinPred

0.011

GERP RS

3.0

Varity_R

0.013

gMVP

0.025

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.11

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over