rs11915740

Positions:

• chr3-57428603-C-A

Variant summary

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

The NM_001366028.2(DNAH12):​c.5253+30G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.396 in 1,510,268 control chromosomes in the GnomAD database, including 124,691 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 0.32 (8780 hom., cov: 32)
  • Exomes 𝑓: 0.40 (115911 hom.)
• Consequence: DNAH12 NM_001366028.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.900

Genes affected

DNAH12 (HGNC:2943): (dynein axonemal heavy chain 12) Predicted to enable several functions, including ATP binding activity; dynein intermediate chain binding activity; and dynein light intermediate chain binding activity. Predicted to be involved in microtubule-based movement. Predicted to be located in cilium; cytoplasm; and microtubule. Predicted to be part of dynein complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.421 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH12	NM_001366028.2	c.5253+30G>T		intron_variant		ENST00000495027.6	NP_001352957.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH12	ENST00000495027.6	c.5253+30G>T		intron_variant		5	NM_001366028.2	ENSP00000418137	P1
DNAH12	ENST00000351747.6	c.5167+47G>T		intron_variant		5		ENSP00000295937

Frequencies

GnomAD3 genomes AF: 0.317 AC: 48103 AN: 151956 Hom.: 8787 Cov.: 32

Gnomad AFR AF: 0.155

Gnomad AMI AF: 0.433

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.0761

Gnomad SAS AF: 0.341

Gnomad FIN AF: 0.401

Gnomad MID AF: 0.370

Gnomad NFE AF: 0.425

Gnomad OTH AF: 0.340

GnomAD3 exomes AF: 0.350 AC: 42821 AN: 122252 Hom.: 8453 AF XY: 0.356 AC XY: 23134 AN XY: 64920

Gnomad AFR exome AF: 0.148

Gnomad AMR exome AF: 0.238

Gnomad ASJ exome AF: 0.409

Gnomad EAS exome AF: 0.0657

Gnomad SAS exome AF: 0.375

Gnomad FIN exome AF: 0.411

Gnomad NFE exome AF: 0.428

Gnomad OTH exome AF: 0.368

GnomAD4 exome AF: 0.405 AC: 549481 AN: 1358194 Hom.: 115911 Cov.: 31 AF XY: 0.404 AC XY: 269734 AN XY: 667228

Gnomad4 AFR exome AF: 0.149

Gnomad4 AMR exome AF: 0.241

Gnomad4 ASJ exome AF: 0.409

Gnomad4 EAS exome AF: 0.0804

Gnomad4 SAS exome AF: 0.369

Gnomad4 FIN exome AF: 0.401

Gnomad4 NFE exome AF: 0.430

Gnomad4 OTH exome AF: 0.377

GnomAD4 genome AF: 0.316 AC: 48121 AN: 152074 Hom.: 8780 Cov.: 32 AF XY: 0.313 AC XY: 23243 AN XY: 74328

Gnomad4 AFR AF: 0.155

Gnomad4 AMR AF: 0.256

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.0761

Gnomad4 SAS AF: 0.340

Gnomad4 FIN AF: 0.401

Gnomad4 NFE AF: 0.425

Gnomad4 OTH AF: 0.335

Alfa AF: 0.401 Hom.: 26463

Bravo AF: 0.298

Asia WGS AF: 0.207 AC: 721 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	6.1
DANN	Benign	0.79

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: rs11915740; hg19: chr3-57414330; COSMIC: COSV61058983;