chr1-1985148-G-T

Variant names:

• chr1-1985148-G-T
• rs3795283
• NM_001304360.2:c.500+238C>A

Variant summary

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

The NM_001304360.2(CFAP74):​c.500+238C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 465,784 control chromosomes in the GnomAD database, including 22,611 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 0.30 (7243 hom., cov: 34)
  • Exomes 𝑓: 0.31 (15368 hom.)
• Consequence: CFAP74 NM_001304360.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800
• Publications: 5 publications found

Genes affected

CFAP74 (HGNC:29368): (cilia and flagella associated protein 74) Predicted to be involved in axoneme assembly. Predicted to be located in axoneme. [provided by Alliance of Genome Resources, Apr 2022]

CFAP74 Gene-Disease associations (from GenCC):

• ciliary dyskinesia, primary, 49, without situs inversus

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics
• primary ciliary dyskinesia

  Inheritance: AR Classification: LIMITED Submitted by: ClinGen

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.335 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CFAP74	NM_001304360.2	c.500+238C>A		intron_variant	Intron 6 of 38	ENST00000682832.2	NP_001291289.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CFAP74	ENST00000682832.2	c.500+238C>A		intron_variant	Intron 6 of 38		NM_001304360.2	ENSP00000508276.2

Frequencies

GnomAD3 genomes AF: 0.303 AC: 46038 AN: 152028 Hom.: 7245 Cov.: 34

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.308

Gnomad AMR AF: 0.263

Gnomad ASJ AF: 0.322

Gnomad EAS AF: 0.337

Gnomad SAS AF: 0.314

Gnomad FIN AF: 0.374

Gnomad MID AF: 0.250

Gnomad NFE AF: 0.339

Gnomad OTH AF: 0.276

GnomAD4 exome AF: 0.309 AC: 96869 AN: 313638 Hom.: 15368 Cov.: 2 AF XY: 0.307 AC XY: 49833 AN XY: 162178

African (AFR) AF: 0.222 AC: 2324 AN: 10478

American (AMR) AF: 0.239 AC: 3735 AN: 15598

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 3469 AN: 10520

East Asian (EAS) AF: 0.331 AC: 8706 AN: 26274

South Asian (SAS) AF: 0.264 AC: 5634 AN: 21330

European-Finnish (FIN) AF: 0.357 AC: 7547 AN: 21164

Middle Eastern (MID) AF: 0.278 AC: 394 AN: 1418

European-Non Finnish (NFE) AF: 0.317 AC: 59560 AN: 188044

Other (OTH) AF: 0.292 AC: 5500 AN: 18812

GnomAD4 genome AF: 0.303 AC: 46040 AN: 152146 Hom.: 7243 Cov.: 34 AF XY: 0.304 AC XY: 22573 AN XY: 74372

African (AFR) AF: 0.235 AC: 9761 AN: 41516

American (AMR) AF: 0.262 AC: 4009 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.322 AC: 1115 AN: 3466

East Asian (EAS) AF: 0.336 AC: 1738 AN: 5166

South Asian (SAS) AF: 0.313 AC: 1514 AN: 4830

European-Finnish (FIN) AF: 0.374 AC: 3956 AN: 10578

Middle Eastern (MID) AF: 0.262 AC: 77 AN: 294

European-Non Finnish (NFE) AF: 0.339 AC: 23011 AN: 67976

Other (OTH) AF: 0.273 AC: 578 AN: 2114

Alfa AF: 0.318 Hom.: 18074

Bravo AF: 0.289

Asia WGS AF: 0.275 AC: 959 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.3
DANN	Benign	0.71
PhyloP100		0.080

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs3795283; hg19: chr1-1916587;