rs1738240

Positions:

• chr6-38795957-C-T

Variant summary

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

The NM_001206927.2(DNAH8):​c.2901+4283C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.647 in 152,022 control chromosomes in the GnomAD database, including 32,181 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 0.65 (32181 hom., cov: 31)
• Consequence: DNAH8 NM_001206927.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.812

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.826 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNAH8	NM_001206927.2	c.2901+4283C>T		intron_variant		ENST00000327475.11	NP_001193856.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNAH8	ENST00000327475.11	c.2901+4283C>T		intron_variant		5	NM_001206927.2	ENSP00000333363.7
DNAH8	ENST00000359357.7	c.2250+4283C>T		intron_variant		2		ENSP00000352312.3
DNAH8	ENST00000449981.6	c.2901+4283C>T		intron_variant		5		ENSP00000415331.2

Frequencies

GnomAD3 genomes AF: 0.647 AC: 98212 AN: 151904 Hom.: 32118 Cov.: 31

Gnomad AFR AF: 0.643

Gnomad AMI AF: 0.640

Gnomad AMR AF: 0.699

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.847

Gnomad SAS AF: 0.682

Gnomad FIN AF: 0.582

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.634

Gnomad OTH AF: 0.620

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

GnomAD4 genome AF: 0.647 AC: 98335 AN: 152022 Hom.: 32181 Cov.: 31 AF XY: 0.646 AC XY: 47961 AN XY: 74284

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.700

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.847

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.582

Gnomad4 NFE AF: 0.634

Gnomad4 OTH AF: 0.623

Alfa AF: 0.638 Hom.: 53338

Bravo AF: 0.657

Asia WGS AF: 0.766 AC: 2666 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	1.3
DANN	Benign	0.84

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: rs1738240; hg19: chr6-38763733;