12-25185340-A-G

Variant names:

• chr12-25185340-A-G
• rs3924649
• NM_018272.5:c.21+5274T>C

Variant summary

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

The NM_018272.5(DNAI7):​c.21+5274T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.403 in 151,936 control chromosomes in the GnomAD database, including 14,228 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 0.40 (14228 hom., cov: 32)
• Consequence: DNAI7 NM_018272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.111
• Publications: 7 publications found

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

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.635 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAI7	NM_018272.5	c.21+5274T>C		intron_variant	Intron 2 of 15	ENST00000395987.8	NP_060742.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAI7	ENST00000395987.8	c.21+5274T>C		intron_variant	Intron 2 of 15	1	NM_018272.5	ENSP00000379310.3

Frequencies

GnomAD3 genomes AF: 0.403 AC: 61136 AN: 151818 Hom.: 14200 Cov.: 32

Gnomad AFR AF: 0.641

Gnomad AMI AF: 0.228

Gnomad AMR AF: 0.346

Gnomad ASJ AF: 0.242

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.246

Gnomad FIN AF: 0.390

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.317

Gnomad OTH AF: 0.373

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

GnomAD4 genome AF: 0.403 AC: 61203 AN: 151936 Hom.: 14228 Cov.: 32 AF XY: 0.398 AC XY: 29581 AN XY: 74254

African (AFR) AF: 0.641 AC: 26562 AN: 41414

American (AMR) AF: 0.346 AC: 5271 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.242 AC: 841 AN: 3470

East Asian (EAS) AF: 0.115 AC: 596 AN: 5184

South Asian (SAS) AF: 0.246 AC: 1185 AN: 4824

European-Finnish (FIN) AF: 0.390 AC: 4115 AN: 10544

Middle Eastern (MID) AF: 0.279 AC: 82 AN: 294

European-Non Finnish (NFE) AF: 0.317 AC: 21564 AN: 67946

Other (OTH) AF: 0.370 AC: 779 AN: 2106

Alfa AF: 0.374 Hom.: 10691

Bravo AF: 0.411

Asia WGS AF: 0.194 AC: 674 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.0
DANN	Benign	0.78
PhyloP100		0.11
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs3924649; hg19: chr12-25338274;