10-122850511-G-A

Variant names:

• chr10-122850511-G-A
• rs1891110
• NM_152644.3:c.5C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.54 (22403 hom., cov: 31)
  • Exomes 𝑓: 0.55 (219707 hom.)
• Consequence: FAM24B NM_152644.3 missense
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.22
• Publications: 50 publications found

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]

ENSG00000286088 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152644.3. 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
	FAM24B	NM_152644.3	MANE Select	c.5C>T	p.Pro2Leu	missense	Exon 3 of 4	NP_689857.2
	FAM24B	NM_001204364.1		c.5C>T	p.Pro2Leu	missense	Exon 3 of 4	NP_001191293.1
	FAM24B	NR_037911.1		n.300-1072C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	ENST00000368898.8	TSL:1 MANE Select	c.5C>T	p.Pro2Leu	missense	Exon 3 of 4	ENSP00000357894.3
	ENSG00000286088	ENST00000368904.6	TSL:1	n.-377-4291C>T		intron	N/A	ENSP00000357900.2
	FAM24B	ENST00000368896.1	TSL:2	c.5C>T	p.Pro2Leu	missense	Exon 3 of 4	ENSP00000357892.1

Frequencies

GnomAD3 genomes AF: 0.541 AC: 82086 AN: 151864 Hom.: 22370 Cov.: 31

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

GnomAD2 exomes AF: 0.530 AC: 133068 AN: 251268 AF XY: 0.531

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 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.: 32 AF XY: 0.545 AC XY: 395378 AN XY: 725110

African (AFR) AF: 0.514 AC: 17157 AN: 33380

American (AMR) AF: 0.454 AC: 20297 AN: 44708

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13571 AN: 26104

East Asian (EAS) AF: 0.526 AC: 20858 AN: 39676

South Asian (SAS) AF: 0.482 AC: 41492 AN: 86160

European-Finnish (FIN) AF: 0.636 AC: 33937 AN: 53402

Middle Eastern (MID) AF: 0.449 AC: 2589 AN: 5762

European-Non Finnish (NFE) AF: 0.555 AC: 614787 AN: 1107572

Other (OTH) AF: 0.536 AC: 32263 AN: 60242

GnomAD4 genome AF: 0.541 AC: 82169 AN: 151980 Hom.: 22403 Cov.: 31 AF XY: 0.542 AC XY: 40301 AN XY: 74290

African (AFR) AF: 0.511 AC: 21161 AN: 41428

American (AMR) AF: 0.503 AC: 7694 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.523 AC: 1817 AN: 3472

East Asian (EAS) AF: 0.508 AC: 2609 AN: 5138

South Asian (SAS) AF: 0.475 AC: 2290 AN: 4826

European-Finnish (FIN) AF: 0.646 AC: 6827 AN: 10568

Middle Eastern (MID) AF: 0.483 AC: 142 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37846 AN: 67962

Other (OTH) AF: 0.530 AC: 1112 AN: 2100

Alfa AF: 0.544 Hom.: 109672

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

Submissions by phenotype

not provided Benign:2

Jan 10, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is associated with the following publications: (PMID: 29083408)

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.047
BayesDel_addAF	Benign	-0.76	T
BayesDel_noAF	Benign	-0.72
CADD	Benign	3.3
DANN	Benign	0.64
DEOGEN2	Benign	0.0032	T
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.00083	N
LIST_S2	Benign	0.28	T
MetaRNN	Benign	0.000016	T
MetaSVM	Benign	-0.93	T
PhyloP100		1.2
PrimateAI	Benign	0.29	T
PROVEAN	Benign	5.0	N
REVEL	Benign	0.067
Sift	Benign	0.70	T
Sift4G	Benign	1.0	T
Polyphen		0.0	B
Vest4		0.020
MPC		0.26
ClinPred		0.011	T
GERP RS		3.0
Varity_R		0.013
gMVP		0.025
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1891110; hg19: chr10-124610027; COSMIC: COSV59026395; COSMIC: COSV59026395;