1-66906378-G-T

Position:

• chr1-66906378-G-T

Variant summary

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

The NM_024763.5(DNAI4):​c.171-1003C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0854 in 151,986 control chromosomes in the GnomAD database, including 748 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 0.085 (748 hom., cov: 31)
• Consequence: DNAI4 NM_024763.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0780

Genes affected

DNAI4 (HGNC:26252): (dynein axonemal intermediate chain 4) Predicted to enable dynein heavy chain binding activity and dynein light chain binding activity. Predicted to be involved in axonemal dynein complex assembly and cilium movement. Predicted to act upstream of or within hematopoietic progenitor cell differentiation. Predicted to be located in axoneme; dynein axonemal particle; and motile cilium. Predicted to be part of axonemal 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.158 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI4	NM_024763.5	c.171-1003C>A		intron_variant		ENST00000371026.8	NP_079039.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI4	ENST00000371026.8	c.171-1003C>A		intron_variant		1	NM_024763.5	ENSP00000360065.3

Frequencies

GnomAD3 genomes AF: 0.0853 AC: 12948 AN: 151868 Hom.: 741 Cov.: 31

Gnomad AFR AF: 0.161

Gnomad AMI AF: 0.0482

Gnomad AMR AF: 0.0634

Gnomad ASJ AF: 0.0447

Gnomad EAS AF: 0.00693

Gnomad SAS AF: 0.0775

Gnomad FIN AF: 0.0458

Gnomad MID AF: 0.111

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0753

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

GnomAD4 genome AF: 0.0854 AC: 12976 AN: 151986 Hom.: 748 Cov.: 31 AF XY: 0.0845 AC XY: 6277 AN XY: 74276

Gnomad4 AFR AF: 0.161

Gnomad4 AMR AF: 0.0632

Gnomad4 ASJ AF: 0.0447

Gnomad4 EAS AF: 0.00695

Gnomad4 SAS AF: 0.0770

Gnomad4 FIN AF: 0.0458

Gnomad4 NFE AF: 0.0597

Gnomad4 OTH AF: 0.0745

Alfa AF: 0.0393 Hom.: 45

Bravo AF: 0.0882

Asia WGS AF: 0.0550 AC: 191 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.61
DANN	Benign	0.45

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs1983860; hg19: chr1-67372061; COSMIC: COSV64018144; COSMIC: COSV64018144;