7-96096252-T-C

Variant names:

• chr7-96096252-T-C
• rs42059
• NM_001135556.2:c.1777-1231T>C

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.1777-1231T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.419 in 151,858 control chromosomes in the GnomAD database, including 14,318 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 0.42 (14318 hom., cov: 32)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.446
• Publications: 3 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=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.504 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1I1	NM_001135556.2	c.1777-1231T>C		intron_variant	Intron 16 of 16	ENST00000447467.6	NP_001129028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC1I1	ENST00000447467.6	c.1777-1231T>C		intron_variant	Intron 16 of 16	1	NM_001135556.2	ENSP00000392337.2

Frequencies

GnomAD3 genomes AF: 0.419 AC: 63574 AN: 151740 Hom.: 14322 Cov.: 32

Gnomad AFR AF: 0.265

Gnomad AMI AF: 0.702

Gnomad AMR AF: 0.404

Gnomad ASJ AF: 0.601

Gnomad EAS AF: 0.321

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.477

Gnomad MID AF: 0.484

Gnomad NFE AF: 0.508

Gnomad OTH AF: 0.460

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

GnomAD4 genome AF: 0.419 AC: 63560 AN: 151858 Hom.: 14318 Cov.: 32 AF XY: 0.414 AC XY: 30705 AN XY: 74182

African (AFR) AF: 0.265 AC: 10975 AN: 41484

American (AMR) AF: 0.404 AC: 6152 AN: 15234

Ashkenazi Jewish (ASJ) AF: 0.601 AC: 2086 AN: 3468

East Asian (EAS) AF: 0.321 AC: 1658 AN: 5162

South Asian (SAS) AF: 0.301 AC: 1450 AN: 4814

European-Finnish (FIN) AF: 0.477 AC: 5030 AN: 10542

Middle Eastern (MID) AF: 0.493 AC: 145 AN: 294

European-Non Finnish (NFE) AF: 0.508 AC: 34466 AN: 67840

Other (OTH) AF: 0.454 AC: 958 AN: 2108

Alfa AF: 0.483 Hom.: 13215

Bravo AF: 0.412

Asia WGS AF: 0.298 AC: 1037 AN: 3466

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	7.5
DANN	Benign	0.75
PhyloP100		0.45
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: rs42059; hg19: chr7-95725564;