NM_018272.5:c.21+3677A>C

Variant names:

• chr12-25186937-T-G
• rs11836162
• NM_018272.5:c.21+3677A>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+3677A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.209 in 152,170 control chromosomes in the GnomAD database, including 5,510 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 0.21 (5510 hom., cov: 32)
• Consequence: DNAI7 NM_018272.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.524
• Publications: 4 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.472 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.21+3677A>C		intron	N/A	NP_060742.4
	DNAI7	NM_001082973.3		c.3+8139A>C		intron	N/A	NP_001076442.2
	DNAI7	NM_001082972.3		c.195+3677A>C		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.21+3677A>C		intron	N/A	ENSP00000379310.3
	DNAI7	ENST00000320267.13	TSL:1	c.3+8139A>C		intron	N/A	ENSP00000313141.9
	DNAI7	ENST00000354189.9	TSL:1	c.195+3677A>C		intron	N/A	ENSP00000346126.5

Frequencies

GnomAD3 genomes AF: 0.209 AC: 31756 AN: 152052 Hom.: 5477 Cov.: 32

Gnomad AFR AF: 0.477

Gnomad AMI AF: 0.112

Gnomad AMR AF: 0.143

Gnomad ASJ AF: 0.195

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.116

Gnomad FIN AF: 0.0417

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.112

Gnomad OTH AF: 0.204

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

GnomAD4 genome AF: 0.209 AC: 31833 AN: 152170 Hom.: 5510 Cov.: 32 AF XY: 0.204 AC XY: 15149 AN XY: 74420

African (AFR) AF: 0.477 AC: 19774 AN: 41446

American (AMR) AF: 0.142 AC: 2177 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.195 AC: 676 AN: 3468

East Asian (EAS) AF: 0.000578 AC: 3 AN: 5188

South Asian (SAS) AF: 0.117 AC: 565 AN: 4832

European-Finnish (FIN) AF: 0.0417 AC: 443 AN: 10618

Middle Eastern (MID) AF: 0.153 AC: 45 AN: 294

European-Non Finnish (NFE) AF: 0.112 AC: 7622 AN: 68004

Other (OTH) AF: 0.202 AC: 426 AN: 2114

Alfa AF: 0.148 Hom.: 3154

Bravo AF: 0.227

Asia WGS AF: 0.0810 AC: 283 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.55
DANN	Benign	0.34
PhyloP100		-0.52
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: rs11836162; hg19: chr12-25339871;