rs36212726

Positions:

• chr10-122879331-T-C

Variant summary

Our verdict is Benign. Variant got -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

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-CUZD1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 50 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.-178+154A>G		intron_variant		ENST00000368898.8	NP_689857.2
FAM24B-CUZD1	NR_037915.1	n.157+154A>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1	c.-148+154A>G		intron_variant			NP_001191293.1
FAM24B	NR_037911.1	n.157+154A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.-178+154A>G		intron_variant		1	NM_152644.3	ENSP00000357894	P1
FAM24B	ENST00000368896.1	c.-148+154A>G		intron_variant		2		ENSP00000357892	P1
FAM24B	ENST00000462859.5	n.157+154A>G		intron_variant, non_coding_transcript_variant		2
FAM24B	ENST00000489000.1	n.97+154A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0219

Gnomad4 AMR AF: 0.0190

Gnomad4 ASJ AF: 0.0233

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.0211

Gnomad4 FIN AF: 0.0141

Gnomad4 NFE AF: 0.0275

Gnomad4 OTH AF: 0.0255

Alfa AF: 0.0280 Hom.: 13

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

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

Publications

LitVar

Other links and lift over

dbSNP: rs36212726; hg19: chr10-124638847;