12-25111325-G-A

Variant names:

• chr12-25111325-G-A
• rs17387019
• NM_018272.5:c.1779+447C>T

Variant summary

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

The NM_018272.5(DNAI7):​c.1779+447C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0566 in 152,212 control chromosomes in the GnomAD database, including 334 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 0.057 (334 hom., cov: 32)
• Consequence: DNAI7 NM_018272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 3 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=-0.9).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0832 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018272.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI7	NM_018272.5	MANE Select	c.1779+447C>T		intron	N/A	NP_060742.4
	DNAI7	NM_001082973.3		c.1761+447C>T		intron	N/A	NP_001076442.2
	DNAI7	NM_001082972.3		c.1953+447C>T		intron	N/A	NP_001076441.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DNAI7	ENST00000395987.8	TSL:1 MANE Select	c.1779+447C>T		intron	N/A	ENSP00000379310.3
	DNAI7	ENST00000320267.13	TSL:1	c.1761+447C>T		intron	N/A	ENSP00000313141.9
	DNAI7	ENST00000354189.9	TSL:1	c.1953+447C>T		intron	N/A	ENSP00000346126.5

Frequencies

GnomAD3 genomes AF: 0.0567 AC: 8617 AN: 152094 Hom.: 333 Cov.: 32

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.0912

Gnomad AMR AF: 0.0739

Gnomad ASJ AF: 0.0928

Gnomad EAS AF: 0.000576

Gnomad SAS AF: 0.0203

Gnomad FIN AF: 0.0313

Gnomad MID AF: 0.0443

Gnomad NFE AF: 0.0850

Gnomad OTH AF: 0.0709

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

GnomAD4 genome AF: 0.0566 AC: 8622 AN: 152212 Hom.: 334 Cov.: 32 AF XY: 0.0541 AC XY: 4024 AN XY: 74430

African (AFR) AF: 0.0172 AC: 714 AN: 41550

American (AMR) AF: 0.0738 AC: 1127 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.0928 AC: 322 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5192

South Asian (SAS) AF: 0.0209 AC: 101 AN: 4826

European-Finnish (FIN) AF: 0.0313 AC: 332 AN: 10596

Middle Eastern (MID) AF: 0.0374 AC: 11 AN: 294

European-Non Finnish (NFE) AF: 0.0850 AC: 5781 AN: 67986

Other (OTH) AF: 0.0701 AC: 148 AN: 2110

Alfa AF: 0.0743 Hom.: 255

Bravo AF: 0.0585

Asia WGS AF: 0.0130 AC: 44 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.042
DANN	Benign	0.42
PhyloP100		-1.5
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: rs17387019; hg19: chr12-25264259;