rs10251970

Variant names:

• chr7-95967520-T-C
• rs10251970
• NM_001135556.2:c.491-9992T>C

Variant summary

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

The NM_001135556.2(DYNC1I1):​c.491-9992T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.472 in 152,004 control chromosomes in the GnomAD database, including 17,256 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 0.47 (17256 hom., cov: 32)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.37

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.519 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1I1	NM_001135556.2	c.491-9992T>C		intron_variant	Intron 6 of 16	ENST00000447467.6	NP_001129028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC1I1	ENST00000447467.6	c.491-9992T>C		intron_variant	Intron 6 of 16	1	NM_001135556.2	ENSP00000392337.2

Frequencies

GnomAD3 genomes AF: 0.472 AC: 71718 AN: 151886 Hom.: 17241 Cov.: 32

Gnomad AFR AF: 0.525

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.457

Gnomad ASJ AF: 0.521

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.349

Gnomad FIN AF: 0.431

Gnomad MID AF: 0.471

Gnomad NFE AF: 0.476

Gnomad OTH AF: 0.457

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

GnomAD4 genome AF: 0.472 AC: 71777 AN: 152004 Hom.: 17256 Cov.: 32 AF XY: 0.467 AC XY: 34726 AN XY: 74288

Gnomad4 AFR AF: 0.525

Gnomad4 AMR AF: 0.457

Gnomad4 ASJ AF: 0.521

Gnomad4 EAS AF: 0.222

Gnomad4 SAS AF: 0.349

Gnomad4 FIN AF: 0.431

Gnomad4 NFE AF: 0.476

Gnomad4 OTH AF: 0.456

Alfa AF: 0.477 Hom.: 4475

Bravo AF: 0.479

Asia WGS AF: 0.309 AC: 1081 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	9.3
DANN	Benign	0.57

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: rs10251970; hg19: chr7-95596832;