rs36212412

Variant names:

• chr10-122862734-A-G
• rs36212412
• NM_152644.3:c.-177-6948T>C

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.-177-6948T>C 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 152,234 control chromosomes in the GnomAD database, including 51 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 (51 hom., cov: 32)
• Consequence: FAM24B NM_152644.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.71
• 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=-0.97).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0147 (2235/152234) while in subpopulation AFR AF = 0.0449 (1863/41530). AF 95% confidence interval is 0.0432. There are 51 homozygotes in GnomAd4. There are 1131 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 51 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FAM24B	NM_152644.3	c.-177-6948T>C		intron_variant	Intron 1 of 3	ENST00000368898.8	NP_689857.2
FAM24B	NM_001204364.1	c.-147-6948T>C		intron_variant	Intron 1 of 3		NP_001191293.1
FAM24B	NR_037911.1	n.158-6948T>C		intron_variant	Intron 1 of 2
FAM24B-CUZD1	NR_037915.1	n.158-6948T>C		intron_variant	Intron 1 of 10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FAM24B	ENST00000368898.8	c.-177-6948T>C		intron_variant	Intron 1 of 3	1	NM_152644.3	ENSP00000357894.3

Frequencies

GnomAD3 genomes AF: 0.0146 AC: 2221 AN: 152116 Hom.: 50 Cov.: 32

Gnomad AFR AF: 0.0447

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00498

Gnomad ASJ AF: 0.0464

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: 0.0147 AC: 2235 AN: 152234 Hom.: 51 Cov.: 32 AF XY: 0.0152 AC XY: 1131 AN XY: 74452

African (AFR) AF: 0.0449 AC: 1863 AN: 41530

American (AMR) AF: 0.00498 AC: 76 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.0464 AC: 161 AN: 3468

East Asian (EAS) AF: 0.0125 AC: 65 AN: 5186

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10608

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: 0.0124 Hom.: 2

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	-0.97
CADD	Benign	0.23
DANN	Benign	0.75
PhyloP100		-1.7
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: rs36212412; hg19: chr10-124622250;