chr10-122879331-T-C

Variant names:

• chr10-122879331-T-C
• rs36212726
• NM_152644.3:c.-178+154A>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.-178+154A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.023 in 152,324 control chromosomes in the GnomAD database, including 50 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 0.023 (50 hom., cov: 32)
• Consequence: FAM24B NM_152644.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• 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=-0.8).
• BS1: Variant frequency is greater than expected in population nfe. GnomAd4 allele frequency = 0.023 (3508/152324) while in subpopulation NFE AF = 0.0275 (1869/68028). AF 95% confidence interval is 0.0264. There are 50 homozygotes in GnomAd4. There are 1643 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.-178+154A>G		intron_variant	Intron 1 of 3	ENST00000368898.8	NP_689857.2
FAM24B	NM_001204364.1	c.-148+154A>G		intron_variant	Intron 1 of 3		NP_001191293.1
FAM24B	NR_037911.1	n.157+154A>G		intron_variant	Intron 1 of 2
FAM24B-CUZD1	NR_037915.1	n.157+154A>G		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.-178+154A>G		intron_variant	Intron 1 of 3	1	NM_152644.3	ENSP00000357894.3

Frequencies

GnomAD3 genomes AF: 0.0230 AC: 3507 AN: 152206 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0220

Gnomad AMI AF: 0.0417

Gnomad AMR AF: 0.0190

Gnomad ASJ AF: 0.0233

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.0211

Gnomad FIN AF: 0.0141

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0275

Gnomad OTH AF: 0.0258

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

GnomAD4 genome AF: 0.0230 AC: 3508 AN: 152324 Hom.: 50 Cov.: 32 AF XY: 0.0221 AC XY: 1643 AN XY: 74492

African (AFR) AF: 0.0219 AC: 910 AN: 41572

American (AMR) AF: 0.0190 AC: 290 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0233 AC: 81 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5182

South Asian (SAS) AF: 0.0211 AC: 102 AN: 4828

European-Finnish (FIN) AF: 0.0141 AC: 150 AN: 10620

Middle Eastern (MID) AF: 0.0442 AC: 13 AN: 294

European-Non Finnish (NFE) AF: 0.0275 AC: 1869 AN: 68028

Other (OTH) AF: 0.0255 AC: 54 AN: 2116

Alfa AF: 0.0261 Hom.: 36

Bravo AF: 0.0229

Asia WGS AF: 0.0120 AC: 43 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	1.9
DANN	Benign	0.59
PhyloP100		-2.6
PromoterAI		-0.075	Neutral
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: rs36212726; hg19: chr10-124638847;