1-85911345-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_152890.7(COL24A1):c.2616+35G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.347 in 1,552,428 control chromosomes in the GnomAD database, including 97,516 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 0.31 (8479 hom., cov: 31)
  • Exomes 𝑓: 0.35 (89037 hom.)
• Consequence: COL24A1 NM_152890.7 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0220

Genes affected

COL24A1 (HGNC:20821): (collagen type XXIV alpha 1 chain) This gene is a member of the collagen gene family and is thought to regulate type I collagen fibrillogenesis during fetal development. [provided by RefSeq, Mar 2017]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
COL24A1	NM_152890.7	c.2616+35G>A		intron_variant		ENST00000370571.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
COL24A1	ENST00000370571.7	c.2616+35G>A		intron_variant		1	NM_152890.7	P1
COL24A1	ENST00000426639.5	c.*66+35G>A		intron_variant, NMD_transcript_variant		5

Frequencies

GnomAD3 genomes AF: 0.314 AC: 47587 AN: 151752 Hom.: 8472 Cov.: 31

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.250

Gnomad AMR AF: 0.436

Gnomad ASJ AF: 0.311

Gnomad EAS AF: 0.509

Gnomad SAS AF: 0.327

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.344

Gnomad NFE AF: 0.343

Gnomad OTH AF: 0.327

GnomAD3 exomes AF: 0.373 AC: 88913 AN: 238184 Hom.: 18015 AF XY: 0.368 AC XY: 47640 AN XY: 129574

Gnomad AFR exome AF: 0.152

Gnomad AMR exome AF: 0.531

Gnomad ASJ exome AF: 0.310

Gnomad EAS exome AF: 0.525

Gnomad SAS exome AF: 0.309

Gnomad FIN exome AF: 0.464

Gnomad NFE exome AF: 0.341

Gnomad OTH exome AF: 0.353

GnomAD4 exome AF: 0.351 AC: 491563 AN: 1400556 Hom.: 89037 Cov.: 23 AF XY: 0.349 AC XY: 244509 AN XY: 700202

Gnomad4 AFR exome AF: 0.158

Gnomad4 AMR exome AF: 0.519

Gnomad4 ASJ exome AF: 0.315

Gnomad4 EAS exome AF: 0.504

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.457

Gnomad4 NFE exome AF: 0.343

Gnomad4 OTH exome AF: 0.343

GnomAD4 genome AF: 0.313 AC: 47605 AN: 151872 Hom.: 8479 Cov.: 31 AF XY: 0.322 AC XY: 23922 AN XY: 74214

Gnomad4 AFR AF: 0.160

Gnomad4 AMR AF: 0.437

Gnomad4 ASJ AF: 0.311

Gnomad4 EAS AF: 0.510

Gnomad4 SAS AF: 0.328

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.343

Gnomad4 OTH AF: 0.323

Alfa AF: 0.326 Hom.: 2476

Bravo AF: 0.308

Asia WGS AF: 0.396 AC: 1376 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	1.7
Dann	Benign	0.43

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: rs10493777; hg19: chr1-86377028; COSMIC: COSV65305391;