7-95804844-C-G

Position:

• chr7-95804844-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001135556.2(DYNC1I1):​c.108+7C>G variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.095 in 1,550,238 control chromosomes in the GnomAD database, including 7,489 homozygotes. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.081 (608 hom., cov: 32)
  • Exomes 𝑓: 0.097 (6881 hom.)
• Consequence: DYNC1I1 NM_001135556.2 splice_region, intron
• Scores: Splicing: ADA: 0.0001070
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -2.52

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

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 7-95804844-C-G is Benign according to our data. Variant chr7-95804844-C-G is described in ClinVar as [Benign]. Clinvar id is 402810.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0974 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DYNC1I1	NM_001135556.2	c.108+7C>G		splice_region_variant, intron_variant		ENST00000447467.6	NP_001129028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DYNC1I1	ENST00000447467.6	c.108+7C>G		splice_region_variant, intron_variant		1	NM_001135556.2	ENSP00000392337.2

Frequencies

GnomAD3 genomes AF: 0.0813 AC: 12341 AN: 151888 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0401

Gnomad AMI AF: 0.240

Gnomad AMR AF: 0.0820

Gnomad ASJ AF: 0.0867

Gnomad EAS AF: 0.0300

Gnomad SAS AF: 0.0707

Gnomad FIN AF: 0.138

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.0994

Gnomad OTH AF: 0.0833

GnomAD3 exomes AF: 0.0846 AC: 13485 AN: 159360 Hom.: 656 AF XY: 0.0854 AC XY: 7187 AN XY: 84148

Gnomad AFR exome AF: 0.0382

Gnomad AMR exome AF: 0.0707

Gnomad ASJ exome AF: 0.0851

Gnomad EAS exome AF: 0.0296

Gnomad SAS exome AF: 0.0764

Gnomad FIN exome AF: 0.127

Gnomad NFE exome AF: 0.0979

Gnomad OTH exome AF: 0.0999

GnomAD4 exome AF: 0.0965 AC: 134933 AN: 1398232 Hom.: 6881 Cov.: 31 AF XY: 0.0959 AC XY: 66208 AN XY: 690064

Gnomad4 AFR exome AF: 0.0402

Gnomad4 AMR exome AF: 0.0715

Gnomad4 ASJ exome AF: 0.0864

Gnomad4 EAS exome AF: 0.0385

Gnomad4 SAS exome AF: 0.0777

Gnomad4 FIN exome AF: 0.129

Gnomad4 NFE exome AF: 0.101

Gnomad4 OTH exome AF: 0.0904

GnomAD4 genome AF: 0.0813 AC: 12351 AN: 152006 Hom.: 608 Cov.: 32 AF XY: 0.0821 AC XY: 6097 AN XY: 74296

Gnomad4 AFR AF: 0.0400

Gnomad4 AMR AF: 0.0821

Gnomad4 ASJ AF: 0.0867

Gnomad4 EAS AF: 0.0304

Gnomad4 SAS AF: 0.0727

Gnomad4 FIN AF: 0.138

Gnomad4 NFE AF: 0.0994

Gnomad4 OTH AF: 0.0825

Alfa AF: 0.0728 Hom.: 165

Bravo AF: 0.0768

Asia WGS AF: 0.0510 AC: 177 AN: 3476

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 12, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 29, 2024	- -

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 29, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

DYNC1I1-related disorder Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 28, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.20
DANN	Benign	0.52

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.00011
dbscSNV1_RF	Benign	0.0060
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: rs41278809; hg19: chr7-95434156;