12-25188243-C-T

Position:

• chr12-25188243-C-T

Variant summary

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

The NM_018272.5(DNAI7):​c.21+2371G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.674 in 152,010 control chromosomes in the GnomAD database, including 36,073 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 0.67 (36073 hom., cov: 31)
• Consequence: DNAI7 NM_018272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.44

Genes affected

DNAI7 (HGNC:29599): (dynein axonemal intermediate chain 7) Predicted to enable beta-tubulin binding activity and microtubule binding activity. Predicted to be located in cilium; cytoplasm; and microtubule cytoskeleton. Predicted to be part of axonemal dynein complex. Predicted to be active in axoneme. [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=-0.84).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAI7	NM_018272.5	c.21+2371G>A		intron_variant		ENST00000395987.8	NP_060742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAI7	ENST00000395987.8	c.21+2371G>A		intron_variant		1	NM_018272.5	ENSP00000379310.3

Frequencies

GnomAD3 genomes AF: 0.674 AC: 102449 AN: 151892 Hom.: 36055 Cov.: 31

Gnomad AFR AF: 0.454

Gnomad AMI AF: 0.795

Gnomad AMR AF: 0.695

Gnomad ASJ AF: 0.794

Gnomad EAS AF: 0.894

Gnomad SAS AF: 0.861

Gnomad FIN AF: 0.695

Gnomad MID AF: 0.766

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.701

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

GnomAD4 genome AF: 0.674 AC: 102506 AN: 152010 Hom.: 36073 Cov.: 31 AF XY: 0.676 AC XY: 50265 AN XY: 74318

Gnomad4 AFR AF: 0.454

Gnomad4 AMR AF: 0.695

Gnomad4 ASJ AF: 0.794

Gnomad4 EAS AF: 0.894

Gnomad4 SAS AF: 0.861

Gnomad4 FIN AF: 0.695

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.704

Alfa AF: 0.749 Hom.: 56490

Bravo AF: 0.662

Asia WGS AF: 0.872 AC: 3033 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.0090
DANN	Benign	0.76

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: rs11047882; hg19: chr12-25341177;