3-52824206-A-G

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_002218.5(ITIH4):​c.1155T>C​(p.Asp385Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000206 in 1,613,272 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00020 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 1 hom. )

Consequence

ITIH4
NM_002218.5 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.47
Variant links:
Genes affected
ITIH4 (HGNC:6169): (inter-alpha-trypsin inhibitor heavy chain 4) The protein encoded by this gene is secreted into the blood, where it is cleaved by plasma kallikrein into two smaller forms. Expression of this gene has been detected only in liver, and it seems to be upregulated during surgical trauma. This gene is part of a cluster of similar genes on chromosome 3. Two transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Oct 2009]
ITIH4-AS1 (HGNC:40310): (ITIH4 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -3 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.41).
BP6
Variant 3-52824206-A-G is Benign according to our data. Variant chr3-52824206-A-G is described in ClinVar as [Benign]. Clinvar id is 764000.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
Synonymous conserved (PhyloP=-1.47 with no splicing effect.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
ITIH4NM_002218.5 linkc.1155T>C p.Asp385Asp synonymous_variant Exon 9 of 24 ENST00000266041.9 NP_002209.2 Q14624-1B7ZKJ8B2RMS9
ITIH4NM_001166449.2 linkc.1155T>C p.Asp385Asp synonymous_variant Exon 9 of 22 NP_001159921.1 Q14624-3B7ZKJ8
ITIH4-AS1NR_046615.1 linkn.154A>G non_coding_transcript_exon_variant Exon 2 of 3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
ITIH4ENST00000266041.9 linkc.1155T>C p.Asp385Asp synonymous_variant Exon 9 of 24 1 NM_002218.5 ENSP00000266041.4 Q14624-1
ENSG00000243696ENST00000468472.1 linkn.*1287T>C non_coding_transcript_exon_variant Exon 14 of 24 2 ENSP00000422253.1 D6R8Y8
ENSG00000243696ENST00000468472.1 linkn.*1287T>C 3_prime_UTR_variant Exon 14 of 24 2 ENSP00000422253.1 D6R8Y8

Frequencies

GnomAD3 genomes
AF:
0.000197
AC:
30
AN:
152170
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000196
Gnomad ASJ
AF:
0.00605
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000882
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.000450
AC:
113
AN:
250920
Hom.:
0
AF XY:
0.000442
AC XY:
60
AN XY:
135710
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.000289
Gnomad ASJ exome
AF:
0.00884
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000970
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000207
AC:
303
AN:
1461102
Hom.:
1
Cov.:
32
AF XY:
0.000219
AC XY:
159
AN XY:
726852
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.000291
Gnomad4 ASJ exome
AF:
0.00876
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000297
Gnomad4 OTH exome
AF:
0.000431
GnomAD4 genome
AF:
0.000197
AC:
30
AN:
152170
Hom.:
0
Cov.:
33
AF XY:
0.000121
AC XY:
9
AN XY:
74326
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000196
Gnomad4 ASJ
AF:
0.00605
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000882
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.00106
Hom.:
0
Bravo
AF:
0.000246
EpiCase
AF:
0.000164
EpiControl
AF:
0.0000593

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jul 18, 2018
Labcorp Genetics (formerly Invitae), Labcorp
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
-0.41
CADD
Benign
0.094
DANN
Benign
0.79

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.060
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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs147858832; hg19: chr3-52858222; API