NM_001206927.2:c.11457+1467G>A

Variant names:

• chr6-38933460-G-A
• rs6458087
• NM_001206927.2:c.11457+1467G>A

Variant summary

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

The NM_001206927.2(DNAH8):​c.11457+1467G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.699 in 152,084 control chromosomes in the GnomAD database, including 37,744 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 0.70 (37744 hom., cov: 32)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.18
• Publications: 2 publications found

Genes affected

DNAH8 (HGNC:2952): (dynein axonemal heavy chain 8) The protein encoded by this gene is a heavy chain of an axonemal dynein involved in sperm and respiratory cilia motility. Axonemal dyneins generate force through hydrolysis of ATP and binding to microtubules. [provided by RefSeq, Jan 2012]

DNAH8-AS1 (HGNC:40188): (DNAH8 antisense RNA 1)

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.812 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.11457+1467G>A		intron_variant	Intron 76 of 92	ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.11457+1467G>A		intron_variant	Intron 76 of 92	5	NM_001206927.2	ENSP00000333363.7

Frequencies

GnomAD3 genomes AF: 0.699 AC: 106200 AN: 151966 Hom.: 37709 Cov.: 32

Gnomad AFR AF: 0.820

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.607

Gnomad ASJ AF: 0.548

Gnomad EAS AF: 0.830

Gnomad SAS AF: 0.668

Gnomad FIN AF: 0.653

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.655

Gnomad OTH AF: 0.649

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

GnomAD4 genome AF: 0.699 AC: 106281 AN: 152084 Hom.: 37744 Cov.: 32 AF XY: 0.696 AC XY: 51765 AN XY: 74336

African (AFR) AF: 0.819 AC: 34025 AN: 41520

American (AMR) AF: 0.607 AC: 9268 AN: 15276

Ashkenazi Jewish (ASJ) AF: 0.548 AC: 1900 AN: 3468

East Asian (EAS) AF: 0.830 AC: 4302 AN: 5184

South Asian (SAS) AF: 0.667 AC: 3210 AN: 4814

European-Finnish (FIN) AF: 0.653 AC: 6892 AN: 10560

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.655 AC: 44530 AN: 67944

Other (OTH) AF: 0.646 AC: 1365 AN: 2114

Alfa AF: 0.665 Hom.: 138918

Bravo AF: 0.700

Asia WGS AF: 0.706 AC: 2455 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.015
DANN	Benign	0.52
PhyloP100		-3.2
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: rs6458087; hg19: chr6-38901236;