rs150647947

Variant names:

• chr3-52824510-T-G
• rs150647947
• NM_002218.5:c.932A>C

Your query was ambiguous. Multiple possible variants found:

• chr3-52824510-T-G
• chr3-52824510-T-A
• chr3-52824510-T-C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_002218.5(ITIH4):​c.932A>C​(p.Asn311Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000014 (0 hom.)
• Consequence: ITIH4 NM_002218.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.913
• Publications: 2 publications found

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]

ENSG00000243696 (HGNC:):

ITIH4-AS1 (HGNC:40310): (ITIH4 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002218.5. 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
	ITIH4	NM_002218.5	MANE Select	c.932A>C	p.Asn311Thr	missense	Exon 8 of 24	NP_002209.2
	ITIH4	NM_001166449.2		c.932A>C	p.Asn311Thr	missense	Exon 8 of 22	NP_001159921.1	Q14624-3
	ITIH4-AS1	NR_046615.1		n.285+173T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ITIH4	ENST00000266041.9	TSL:1 MANE Select	c.932A>C	p.Asn311Thr	missense	Exon 8 of 24	ENSP00000266041.4	Q14624-1
	ITIH4	ENST00000485816.5	TSL:1	c.932A>C	p.Asn311Thr	missense	Exon 8 of 24	ENSP00000417824.1	B7ZKJ8
	ITIH4	ENST00000441637.2	TSL:1	c.503A>C	p.Asn168Thr	missense	Exon 5 of 18	ENSP00000395634.2	H7C0L5

Frequencies

GnomAD3 genomes AF: 0.000158 AC: 24 AN: 152136 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000580

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000438 AC: 11 AN: 251404 AF XY: 0.0000294

Gnomad AFR exome AF: 0.000369

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000272

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000144 AC: 21 AN: 1461826 Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7 AN XY: 727226

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000504 AC: 2 AN: 39700

South Asian (SAS) AF: 0.0000116 AC: 1 AN: 86256

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53364

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.000166 AC: 10 AN: 60394

GnomAD4 genome AF: 0.000158 AC: 24 AN: 152136 Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74308

African (AFR) AF: 0.000580 AC: 24 AN: 41414

American (AMR) AF: 0.00 AC: 0 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10614

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68018

Other (OTH) AF: 0.00 AC: 0 AN: 2094

Alfa AF: 0.000106 Hom.: 0

Bravo AF: 0.000132

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000659 AC: 8

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.75	D
Eigen	Benign	-0.10
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Benign	0.80	T
M_CAP	Uncertain	0.17	D
MetaRNN	Uncertain	0.74	D
MetaSVM	Benign	-0.69	T
MutationAssessor	Uncertain	2.8	M
PhyloP100		0.91
PrimateAI	Benign	0.43	T
PROVEAN	Pathogenic	-5.4	D
REVEL	Uncertain	0.58
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.014	D
Polyphen		0.98	D
Vest4		0.72
MVP		0.79
MPC		0.95
ClinPred		0.42	T
GERP RS		2.6
Varity_R		0.40
gMVP		0.53
Mutation Taster		=55/45	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs150647947; hg19: chr3-52858526;