chr10-122852435-A-T

Variant names:

• chr10-122852435-A-T
• rs36212410
• NM_152644.3:c.-35-1885T>A

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.-35-1885T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0149 in 152,306 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: 0.0130
• 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=-1.03).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0149 (2275/152306) while in subpopulation AFR AF = 0.0458 (1903/41566). AF 95% confidence interval is 0.0441. There are 54 homozygotes in GnomAd4. There are 1146 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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.-35-1885T>A		intron_variant	Intron 2 of 3	ENST00000368898.8	NP_689857.2
FAM24B	NM_001204364.1	c.-5-1915T>A		intron_variant	Intron 2 of 3		NP_001191293.1
FAM24B	NR_037911.1	n.300-2996T>A		intron_variant	Intron 2 of 2
FAM24B-CUZD1	NR_037915.1	n.299+3210T>A		intron_variant	Intron 2 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.-35-1885T>A		intron_variant	Intron 2 of 3	1	NM_152644.3	ENSP00000357894.3
ENSG00000286088	ENST00000368904.6	n.-378+3210T>A		intron_variant	Intron 1 of 9	1		ENSP00000357900.2

Frequencies

GnomAD3 genomes AF: 0.0149 AC: 2261 AN: 152188 Hom.: 53 Cov.: 32

Gnomad AFR AF: 0.0456

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00504

Gnomad ASJ AF: 0.0461

Gnomad EAS AF: 0.0125

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: 0.0149 AC: 2275 AN: 152306 Hom.: 54 Cov.: 32 AF XY: 0.0154 AC XY: 1146 AN XY: 74476

African (AFR) AF: 0.0458 AC: 1903 AN: 41566

American (AMR) AF: 0.00503 AC: 77 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.0461 AC: 160 AN: 3468

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5182

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10620

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

European-Non Finnish (NFE) AF: 0.000735 AC: 50 AN: 68018

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

Alfa AF: 0.0107 Hom.: 3

Bravo AF: 0.0170

Asia WGS AF: 0.0130 AC: 45 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.7
DANN	Benign	0.69
PhyloP100		0.013
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: rs36212410; hg19: chr10-124611951;