NM_001135556.2:c.1777-859A>G

Variant names:

• chr7-96096624-A-G
• rs916758
• NM_001135556.2:c.1777-859A>G

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.1777-859A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.206 in 152,020 control chromosomes in the GnomAD database, including 3,709 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 (3709 hom., cov: 32)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.625
• Publications: 5 publications found

Genes affected

DYNC1I1 (HGNC:2963): (dynein cytoplasmic 1 intermediate chain 1) Enables spectrin binding activity. Involved in vesicle transport along microtubule. Located in several cellular components, including kinetochore; recycling endosome; and spindle pole. [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=-0.57).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.361 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001135556.2. 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
	DYNC1I1	NM_001135556.2	MANE Select	c.1777-859A>G		intron	N/A	NP_001129028.1
	DYNC1I1	NM_004411.5		c.1828-859A>G		intron	N/A	NP_004402.1
	DYNC1I1	NM_001278421.2		c.1768-859A>G		intron	N/A	NP_001265350.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.1777-859A>G		intron	N/A	ENSP00000392337.2
	DYNC1I1	ENST00000324972.10	TSL:1	c.1828-859A>G		intron	N/A	ENSP00000320130.6
	DYNC1I1	ENST00000457059.2	TSL:1	c.1777-859A>G		intron	N/A	ENSP00000412444.1

Frequencies

GnomAD3 genomes AF: 0.206 AC: 31260 AN: 151902 Hom.: 3686 Cov.: 32

Gnomad AFR AF: 0.293

Gnomad AMI AF: 0.129

Gnomad AMR AF: 0.267

Gnomad ASJ AF: 0.0758

Gnomad EAS AF: 0.375

Gnomad SAS AF: 0.205

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.146

Gnomad OTH AF: 0.192

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

GnomAD4 genome AF: 0.206 AC: 31341 AN: 152020 Hom.: 3709 Cov.: 32 AF XY: 0.208 AC XY: 15437 AN XY: 74296

African (AFR) AF: 0.293 AC: 12157 AN: 41462

American (AMR) AF: 0.268 AC: 4086 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0758 AC: 263 AN: 3470

East Asian (EAS) AF: 0.375 AC: 1936 AN: 5162

South Asian (SAS) AF: 0.205 AC: 985 AN: 4814

European-Finnish (FIN) AF: 0.136 AC: 1437 AN: 10594

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

European-Non Finnish (NFE) AF: 0.146 AC: 9893 AN: 67954

Other (OTH) AF: 0.200 AC: 421 AN: 2108

Alfa AF: 0.162 Hom.: 9521

Bravo AF: 0.217

Asia WGS AF: 0.297 AC: 1033 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	10
DANN	Benign	0.61
PhyloP100		0.63
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: rs916758; hg19: chr7-95725936;