9-128208739-A-G

Position:

• chr9-128208739-A-G

Variant summary

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

The NM_004408.4(DNM1):​c.161+5108A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.114 in 152,004 control chromosomes in the GnomAD database, including 1,649 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 0.11 (1649 hom., cov: 31)
• Consequence: DNM1 NM_004408.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.482

Genes affected

DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4	c.161+5108A>G		intron_variant		ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8	c.161+5108A>G		intron_variant		1	NM_004408.4	A1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17362 AN: 151886 Hom.: 1646 Cov.: 31

Gnomad AFR AF: 0.233

Gnomad AMI AF: 0.0548

Gnomad AMR AF: 0.0725

Gnomad ASJ AF: 0.0213

Gnomad EAS AF: 0.356

Gnomad SAS AF: 0.110

Gnomad FIN AF: 0.0800

Gnomad MID AF: 0.0382

Gnomad NFE AF: 0.0452

Gnomad OTH AF: 0.0999

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

GnomAD4 genome AF: 0.114 AC: 17377 AN: 152004 Hom.: 1649 Cov.: 31 AF XY: 0.116 AC XY: 8637 AN XY: 74282

Gnomad4 AFR AF: 0.233

Gnomad4 AMR AF: 0.0723

Gnomad4 ASJ AF: 0.0213

Gnomad4 EAS AF: 0.355

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0800

Gnomad4 NFE AF: 0.0452

Gnomad4 OTH AF: 0.0993

Alfa AF: 0.0789 Hom.: 284

Bravo AF: 0.120

Asia WGS AF: 0.192 AC: 669 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	2.2
DANN	Benign	0.74

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs7875406; hg19: chr9-130971018;