4-17632593-T-G

Variant names:

• chr4-17632593-T-G
• rs916540890
• NM_015688.2:c.3122A>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_015688.2(FAM184B):​c.3122A>C​(p.Glu1041Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000245 in 1,551,234 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 34)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: FAM184B NM_015688.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.58
• Publications: 0 publications found

Genes affected

FAM184B (HGNC:29235): (family with sequence similarity 184 member B)

MED28 (HGNC:24628): (mediator complex subunit 28) Predicted to enable actin binding activity. Predicted to act upstream of or within negative regulation of smooth muscle cell differentiation and stem cell population maintenance. Located in nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.05810049).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015688.2. 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
	FAM184B	NM_015688.2	MANE Select	c.3122A>C	p.Glu1041Ala	missense	Exon 18 of 18	NP_056503.1	Q9ULE4
	MED28	NM_025205.5	MANE Select	c.*8795T>G		3_prime_UTR	Exon 4 of 4	NP_079481.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FAM184B	ENST00000265018.4	TSL:1 MANE Select	c.3122A>C	p.Glu1041Ala	missense	Exon 18 of 18	ENSP00000265018.3	Q9ULE4
	MED28	ENST00000237380.12	TSL:1 MANE Select	c.*8795T>G		3_prime_UTR	Exon 4 of 4	ENSP00000237380.6	Q9H204
	FAM184B	ENST00000954035.1		c.3011A>C	p.Glu1004Ala	missense	Exon 17 of 17	ENSP00000624094.1

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152172 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00105

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: 0.0000320 AC: 5 AN: 156476 AF XY: 0.0000362

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000162

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000157 AC: 22 AN: 1399062 Hom.: 0 Cov.: 34 AF XY: 0.0000130 AC XY: 9 AN XY: 690064

African (AFR) AF: 0.0000317 AC: 1 AN: 31588

American (AMR) AF: 0.000252 AC: 9 AN: 35672

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25168

East Asian (EAS) AF: 0.00 AC: 0 AN: 35730

South Asian (SAS) AF: 0.0000379 AC: 3 AN: 79228

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 49244

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5692

European-Non Finnish (NFE) AF: 0.00000742 AC: 8 AN: 1078754

Other (OTH) AF: 0.0000172 AC: 1 AN: 57986

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152172 Hom.: 0 Cov.: 34 AF XY: 0.000161 AC XY: 12 AN XY: 74340

African (AFR) AF: 0.00 AC: 0 AN: 41456

American (AMR) AF: 0.00105 AC: 16 AN: 15262

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4830

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68034

Other (OTH) AF: 0.00 AC: 0 AN: 2088

Alfa AF: 0.0000282 Hom.: 0

Bravo AF: 0.000102

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	0.089
BayesDel_addAF	Benign	-0.37	T
BayesDel_noAF	Benign	-0.51
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.71	T
M_CAP	Benign	0.023	T
MetaRNN	Benign	0.058	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Uncertain	2.1	M
PhyloP100		1.6
PrimateAI	Benign	0.44	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.084
Sift	Uncertain	0.010	D
Sift4G	Benign	0.20	T
Polyphen		0.97	D
Vest4		0.17
MutPred		0.064		Loss of glycosylation at K1040 (P = 0.0643)
MVP		0.11
ClinPred		0.25	T
GERP RS		5.5
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.15
gMVP		0.21
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: rs916540890; hg19: chr4-17634216;