rs3740798

Variant names:

• chr11-35685232-G-C
• rs3740798
• NM_017583.6:c.670-27G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-35685232-G-C
• chr11-35685232-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017583.6(TRIM44):​c.670-27G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.149 in 1,596,814 control chromosomes in the GnomAD database, including 18,953 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.12 (1416 hom., cov: 33)
  • Exomes 𝑓: 0.15 (17537 hom.)
• Consequence: TRIM44 NM_017583.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.99
• Publications: 8 publications found

Genes affected

TRIM44 (HGNC:19016): (tripartite motif containing 44) This gene encodes a member of the tripartite motif (TRIM) family. The TRIM motif includes three zinc-binding domains, namely a RING, a B-box type 1 and a B-box type 2, and a coiled-coil region. [provided by RefSeq, Jul 2008]

TRIM44 Gene-Disease associations (from GenCC):

• isolated aniridia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• aniridia 3

  Inheritance: AD Classification: LIMITED Submitted by: G2P, Labcorp Genetics (formerly Invitae), Genomics England PanelApp, Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: This position, referring to a specific DNA site, is a probable branch point but is likely benign (scored 3 / 10, using the threshold of <=3). The score ranges from 0 to 10, with values ≤3 considered benign and >5 classified as pathogenic. Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 11-35685232-G-C is Benign according to our data. Variant chr11-35685232-G-C is described in ClinVar as Benign. ClinVar VariationId is 1342269.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.165 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
TRIM44	NM_017583.6	c.670-27G>C		intron_variant	Intron 1 of 4	ENST00000299413.7	NP_060053.2
TRIM44	XM_006718254.2	c.670-27G>C		intron_variant	Intron 1 of 3		XP_006718317.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
TRIM44	ENST00000299413.7	c.670-27G>C		intron_variant	Intron 1 of 4	1	NM_017583.6	ENSP00000299413.5

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18668 AN: 152174 Hom.: 1413 Cov.: 33

Gnomad AFR AF: 0.0426

Gnomad AMI AF: 0.0593

Gnomad AMR AF: 0.106

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.0650

Gnomad SAS AF: 0.102

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.168

Gnomad OTH AF: 0.131

GnomAD2 exomes AF: 0.137 AC: 34199 AN: 249668 AF XY: 0.140

Gnomad AFR exome AF: 0.0387

Gnomad AMR exome AF: 0.109

Gnomad ASJ exome AF: 0.117

Gnomad EAS exome AF: 0.0611

Gnomad FIN exome AF: 0.216

Gnomad NFE exome AF: 0.168

Gnomad OTH exome AF: 0.146

GnomAD4 exome AF: 0.152 AC: 219423 AN: 1444522 Hom.: 17537 Cov.: 27 AF XY: 0.151 AC XY: 109042 AN XY: 719780

African (AFR) AF: 0.0335 AC: 1110 AN: 33114

American (AMR) AF: 0.111 AC: 4913 AN: 44352

Ashkenazi Jewish (ASJ) AF: 0.114 AC: 2971 AN: 25996

East Asian (EAS) AF: 0.0753 AC: 2981 AN: 39598

South Asian (SAS) AF: 0.105 AC: 9001 AN: 85418

European-Finnish (FIN) AF: 0.221 AC: 11816 AN: 53396

Middle Eastern (MID) AF: 0.117 AC: 669 AN: 5726

European-Non Finnish (NFE) AF: 0.162 AC: 177551 AN: 1097150

Other (OTH) AF: 0.141 AC: 8411 AN: 59772

GnomAD4 genome AF: 0.123 AC: 18682 AN: 152292 Hom.: 1416 Cov.: 33 AF XY: 0.124 AC XY: 9230 AN XY: 74478

African (AFR) AF: 0.0425 AC: 1767 AN: 41588

American (AMR) AF: 0.106 AC: 1615 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3472

East Asian (EAS) AF: 0.0652 AC: 338 AN: 5188

South Asian (SAS) AF: 0.103 AC: 498 AN: 4824

European-Finnish (FIN) AF: 0.218 AC: 2306 AN: 10602

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.168 AC: 11391 AN: 67998

Other (OTH) AF: 0.136 AC: 288 AN: 2114

Alfa AF: 0.0987 Hom.: 211

Bravo AF: 0.110

Asia WGS AF: 0.0870 AC: 300 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Aniridia 3 Benign:1

Sep 10, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	12
DANN	Benign	0.44
PhyloP100		2.0
BranchPoint Hunter		3.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		1.0
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: rs3740798; hg19: chr11-35706780;