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. The variant received -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
• Publications: 0 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 -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.091 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	NM_001135556.2	MANE Select	c.224-141_224-140dupTT		intron	N/A	NP_001129028.1	O14576-2
	DYNC1I1	NM_004411.5		c.224-90_224-89dupTT		intron	N/A	NP_004402.1	O14576-1
	DYNC1I1	NM_001278421.2		c.224-90_224-89dupTT		intron	N/A	NP_001265350.1	O14576-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DYNC1I1	ENST00000447467.6	TSL:1 MANE Select	c.224-154_224-153insTT		intron	N/A	ENSP00000392337.2	O14576-2
	DYNC1I1	ENST00000324972.10	TSL:1	c.224-103_224-102insTT		intron	N/A	ENSP00000320130.6	O14576-1
	DYNC1I1	ENST00000457059.2	TSL:1	c.224-154_224-153insTT		intron	N/A	ENSP00000412444.1	O14576-2

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.117 AC: 2170 AN: 18540

American (AMR) AF: 0.0520 AC: 901 AN: 17316

Ashkenazi Jewish (ASJ) AF: 0.0288 AC: 482 AN: 16738

East Asian (EAS) AF: 0.0586 AC: 1533 AN: 26178

South Asian (SAS) AF: 0.0388 AC: 1907 AN: 49156

European-Finnish (FIN) AF: 0.0371 AC: 1122 AN: 30206

Middle Eastern (MID) AF: 0.0333 AC: 97 AN: 2912

European-Non Finnish (NFE) AF: 0.0345 AC: 26341 AN: 763716

Other (OTH) AF: 0.0413 AC: 1652 AN: 39970

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

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

African (AFR) AF: 0.0935 AC: 3569 AN: 38152

American (AMR) AF: 0.0118 AC: 164 AN: 13884

Ashkenazi Jewish (ASJ) AF: 0.000888 AC: 3 AN: 3380

East Asian (EAS) AF: 0.00973 AC: 47 AN: 4830

South Asian (SAS) AF: 0.00289 AC: 13 AN: 4496

European-Finnish (FIN) AF: 0.000423 AC: 3 AN: 7086

Middle Eastern (MID) AF: 0.00741 AC: 2 AN: 270

European-Non Finnish (NFE) AF: 0.00119 AC: 78 AN: 65398

Other (OTH) AF: 0.0222 AC: 43 AN: 1936

Alfa AF: 0.00 Hom.: 272

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.36
Mutation Taster		=99/1	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs11452827; hg19: chr7-95442405;