7-95813093-CTTTTT-CTTTTTTT

Variant names:

• chr7-95813093-C-CTT
• rs11452827
• NM_001135556.2:c.224-141_224-140dupTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001135556.2(DYNC1I1):​c.224-141_224-140dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0363 in 1,105,056 control chromosomes in the GnomAD database, including 327 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.028 (185 hom., cov: 0)
  • Exomes 𝑓: 0.038 (142 hom.)
• Consequence: DYNC1I1 NM_001135556.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.361

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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DYNC1I1	NM_001135556.2	c.224-141_224-140dupTT		intron_variant	Intron 3 of 16	ENST00000447467.6	NP_001129028.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DYNC1I1	ENST00000447467.6	c.224-154_224-153insTT		intron_variant	Intron 3 of 16	1	NM_001135556.2	ENSP00000392337.2

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 3921 AN: 140312 Hom.: 185 Cov.: 0

Gnomad AFR AF: 0.0936

Gnomad AMI AF: 0.00448

Gnomad AMR AF: 0.0118

Gnomad ASJ AF: 0.000888

Gnomad EAS AF: 0.00970

Gnomad SAS AF: 0.00287

Gnomad FIN AF: 0.000423

Gnomad MID AF: 0.00680

Gnomad NFE AF: 0.00119

Gnomad OTH AF: 0.0224

GnomAD4 exome AF: 0.0375 AC: 36205 AN: 964732 Hom.: 142 AF XY: 0.0375 AC XY: 18001 AN XY: 480180

Gnomad4 AFR exome AF: 0.117

Gnomad4 AMR exome AF: 0.0520

Gnomad4 ASJ exome AF: 0.0288

Gnomad4 EAS exome AF: 0.0586

Gnomad4 SAS exome AF: 0.0388

Gnomad4 FIN exome AF: 0.0371

Gnomad4 NFE exome AF: 0.0345

Gnomad4 OTH exome AF: 0.0413

GnomAD4 genome AF: 0.0280 AC: 3926 AN: 140324 Hom.: 185 Cov.: 0 AF XY: 0.0280 AC XY: 1889 AN XY: 67554

Gnomad4 AFR AF: 0.0935

Gnomad4 AMR AF: 0.0118

Gnomad4 ASJ AF: 0.000888

Gnomad4 EAS AF: 0.00973

Gnomad4 SAS AF: 0.00289

Gnomad4 FIN AF: 0.000423

Gnomad4 NFE AF: 0.00119

Gnomad4 OTH AF: 0.0222

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11452827; hg19: chr7-95442405;