chr10-122863143-T-C

Variant names:

• chr10-122863143-T-C
• rs36212725
• NM_152644.3:c.-177-7357A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_152644.3(FAM24B):​c.-177-7357A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0147 in 152,292 control chromosomes in the GnomAD database, including 54 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.015 (54 hom., cov: 32)
• Consequence: FAM24B NM_152644.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.325
• Publications: 0 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2244/152292) while in subpopulation AFR AF = 0.045 (1872/41558). AF 95% confidence interval is 0.0433. There are 54 homozygotes in GnomAd4. There are 1130 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

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.-177-7357A>G		intron	N/A	NP_689857.2
	FAM24B	NM_001204364.1		c.-147-7357A>G		intron	N/A	NP_001191293.1
	FAM24B	NR_037911.1		n.158-7357A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM24B	ENST00000368898.8	TSL:1 MANE Select	c.-177-7357A>G		intron	N/A	ENSP00000357894.3
	FAM24B	ENST00000368896.1	TSL:2	c.-147-7357A>G		intron	N/A	ENSP00000357892.1
	FAM24B	ENST00000462859.5	TSL:2	n.158-7357A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0147 AC: 2230 AN: 152174 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0449

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0464

Gnomad EAS AF: 0.0123

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000735

Gnomad OTH AF: 0.00574

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0147 AC: 2244 AN: 152292 Hom.: 54 Cov.: 32 AF XY: 0.0152 AC XY: 1130 AN XY: 74456

African (AFR) AF: 0.0450 AC: 1872 AN: 41558

American (AMR) AF: 0.00503 AC: 77 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3472

East Asian (EAS) AF: 0.0124 AC: 64 AN: 5176

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68020

Other (OTH) AF: 0.00710 AC: 15 AN: 2114

Alfa AF: 0.00376 Hom.: 3

Bravo AF: 0.0169

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.57
PhyloP100		-0.33
Mutation Taster		=100/0	polymorphism

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: rs36212725; hg19: chr10-124622659;