rs12992408

Variant names:

• chr2-55521949-T-G
• rs12992408
• NM_080667.7:c.116-153T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_080667.7(CFAP36):​c.116-153T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,008 control chromosomes in the GnomAD database, including 3,900 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 0.22 (3900 hom., cov: 32)
• Consequence: CFAP36 NM_080667.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.333
• Publications: 5 publications found

Genes affected

CFAP36 (HGNC:30540): (cilia and flagella associated protein 36) Enables protein N-terminus binding activity. Located in ciliary transition zone. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.326 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP36	NM_080667.7	c.116-153T>G		intron_variant	Intron 1 of 9	ENST00000349456.9	NP_542398.3
CFAP36	NM_001282761.2	c.191-153T>G		intron_variant	Intron 2 of 10		NP_001269690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP36	ENST00000349456.9	c.116-153T>G		intron_variant	Intron 1 of 9	1	NM_080667.7	ENSP00000295117.4

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33827 AN: 151890 Hom.: 3891 Cov.: 32

Gnomad AFR AF: 0.242

Gnomad AMI AF: 0.287

Gnomad AMR AF: 0.235

Gnomad ASJ AF: 0.256

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.254

Gnomad FIN AF: 0.212

Gnomad MID AF: 0.185

Gnomad NFE AF: 0.196

Gnomad OTH AF: 0.227

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

GnomAD4 genome AF: 0.223 AC: 33856 AN: 152008 Hom.: 3900 Cov.: 32 AF XY: 0.224 AC XY: 16635 AN XY: 74328

African (AFR) AF: 0.242 AC: 10016 AN: 41442

American (AMR) AF: 0.235 AC: 3595 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.256 AC: 889 AN: 3468

East Asian (EAS) AF: 0.339 AC: 1754 AN: 5168

South Asian (SAS) AF: 0.253 AC: 1219 AN: 4824

European-Finnish (FIN) AF: 0.212 AC: 2234 AN: 10540

Middle Eastern (MID) AF: 0.168 AC: 49 AN: 292

European-Non Finnish (NFE) AF: 0.197 AC: 13359 AN: 67982

Other (OTH) AF: 0.227 AC: 479 AN: 2106

Alfa AF: 0.208 Hom.: 8648

Bravo AF: 0.229

Asia WGS AF: 0.268 AC: 931 AN: 3468

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.7
DANN	Benign	0.68
PhyloP100		0.33
Mutation Taster		=100/0	polymorphism (auto)

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: rs12992408; hg19: chr2-55749085; COSMIC: COSV107441464;