rs4944178

Variant names:

• chr11-77882175-C-T
• rs4944178
• NM_033547.4:c.2713+1657G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_033547.4(INTS4):​c.2713+1657G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 152,110 control chromosomes in the GnomAD database, including 1,453 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1453 hom., cov: 31)
• Consequence: INTS4 NM_033547.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.305
• Publications: 9 publications found

Genes affected

INTS4 (HGNC:25048): (integrator complex subunit 4) INTS4 is a subunit of the Integrator complex, which associates with the C-terminal domain of RNA polymerase II large subunit (POLR2A; MIM 180660) and mediates 3-prime end processing of small nuclear RNAs U1 (RNU1; MIM 180680) and U2 (RNU2; MIM 180690) (Baillat et al., 2005 [PubMed 16239144]).[supplied by OMIM, Mar 2008]

AAMDC (HGNC:30205): (adipogenesis associated Mth938 domain containing) Predicted to be involved in positive regulation of fat cell differentiation. Predicted to act upstream of or within negative regulation of apoptotic process and positive regulation of transcription by RNA polymerase II. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.19 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_033547.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS4	NM_033547.4	MANE Select	c.2713+1657G>A		intron	N/A	NP_291025.3
	AAMDC	NM_001316957.3		c.328+5126C>T		intron	N/A	NP_001303886.1
	AAMDC	NM_001316958.3		c.383+3419C>T		intron	N/A	NP_001303887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	INTS4	ENST00000534064.6	TSL:1 MANE Select	c.2713+1657G>A		intron	N/A	ENSP00000434466.1
	AAMDC	ENST00000304716.12	TSL:1	c.328+5126C>T		intron	N/A	ENSP00000307254.8
	AAMDC	ENST00000532481.5	TSL:1	c.228+12358C>T		intron	N/A	ENSP00000433293.1

Frequencies

GnomAD3 genomes AF: 0.129 AC: 19662 AN: 151992 Hom.: 1448 Cov.: 31

Gnomad AFR AF: 0.130

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.195

Gnomad ASJ AF: 0.0890

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.127

Gnomad FIN AF: 0.218

Gnomad MID AF: 0.0380

Gnomad NFE AF: 0.100

Gnomad OTH AF: 0.111

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.129 AC: 19695 AN: 152110 Hom.: 1453 Cov.: 31 AF XY: 0.135 AC XY: 10025 AN XY: 74340

African (AFR) AF: 0.130 AC: 5411 AN: 41500

American (AMR) AF: 0.195 AC: 2987 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0890 AC: 309 AN: 3470

East Asian (EAS) AF: 0.179 AC: 922 AN: 5164

South Asian (SAS) AF: 0.128 AC: 617 AN: 4826

European-Finnish (FIN) AF: 0.218 AC: 2302 AN: 10548

Middle Eastern (MID) AF: 0.0408 AC: 12 AN: 294

European-Non Finnish (NFE) AF: 0.100 AC: 6826 AN: 67996

Other (OTH) AF: 0.115 AC: 242 AN: 2110

Alfa AF: 0.108 Hom.: 442

Bravo AF: 0.130

Asia WGS AF: 0.165 AC: 571 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.81
PhyloP100		0.30
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
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: rs4944178; hg19: chr11-77593221;