rs36212725

Positions:

• chr10-122863143-T-C
• chr10-122863143-T-G

Variant summary

Our verdict is Benign. Variant got -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

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=-0.96).
• 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 male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 54 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.-177-7357A>G		intron_variant		ENST00000368898.8	NP_689857.2
FAM24B-CUZD1	NR_037915.1	n.158-7357A>G		intron_variant, non_coding_transcript_variant
FAM24B	NM_001204364.1	c.-147-7357A>G		intron_variant			NP_001191293.1
FAM24B	NR_037911.1	n.158-7357A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.-177-7357A>G		intron_variant		1	NM_152644.3	ENSP00000357894	P1
FAM24B	ENST00000368896.1	c.-147-7357A>G		intron_variant		2		ENSP00000357892	P1
FAM24B	ENST00000462859.5	n.158-7357A>G		intron_variant, non_coding_transcript_variant		2
FAM24B	ENST00000489000.1	n.98-7357A>G		intron_variant, non_coding_transcript_variant		2

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

Gnomad4 AFR AF: 0.0450

Gnomad4 AMR AF: 0.00503

Gnomad4 ASJ AF: 0.0464

Gnomad4 EAS AF: 0.0124

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000735

Gnomad4 OTH AF: 0.00710

Alfa AF: 0.00236 Hom.: 3

Bravo AF: 0.0169

Asia WGS AF: 0.0140 AC: 47 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	0.20
DANN	Benign	0.57

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: rs36212725; hg19: chr10-124622659;