2-238140983-C-A

Variant names:

• chr2-238140983-C-A
• rs375615704
• NM_198582.4:c.229C>A

Variant summary

Our verdict is Benign. The variant received -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_198582.4(KLHL30):​c.229C>A​(p.Arg77Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,612,428 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00092 (0 hom., cov: 34)
  • Exomes 𝑓: 0.0018 (2 hom.)
• Consequence: KLHL30 NM_198582.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59
• Publications: 0 publications found

Genes affected

KLHL30 (HGNC:24770): (kelch like family member 30)

ACMG classification

Our verdict: Benign. The variant received -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BP6: Variant 2-238140983-C-A is Benign according to our data. Variant chr2-238140983-C-A is described in ClinVar as Likely_benign. ClinVar VariationId is 2652061.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=1.59 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 2 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_198582.4. 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
	KLHL30	NM_198582.4	MANE Select	c.229C>A	p.Arg77Arg	synonymous	Exon 2 of 8	NP_940984.3	Q0D2K2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLHL30	ENST00000409223.2	TSL:5 MANE Select	c.229C>A	p.Arg77Arg	synonymous	Exon 2 of 8	ENSP00000386389.1	Q0D2K2
	KLHL30	ENST00000964872.1		c.229C>A	p.Arg77Arg	synonymous	Exon 2 of 7	ENSP00000634931.1
	KLHL30	ENST00000964871.1		c.229C>A	p.Arg77Arg	synonymous	Exon 2 of 7	ENSP00000634930.1

Frequencies

GnomAD3 genomes AF: 0.000920 AC: 140 AN: 152246 Hom.: 0 Cov.: 34

Gnomad AFR AF: 0.000362

Gnomad AMI AF: 0.00329

Gnomad AMR AF: 0.000785

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000847

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00147

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.000999 AC: 247 AN: 247314 AF XY: 0.00103

Gnomad AFR exome AF: 0.000260

Gnomad AMR exome AF: 0.00107

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.000836

Gnomad NFE exome AF: 0.00163

Gnomad OTH exome AF: 0.00116

GnomAD4 exome AF: 0.00184 AC: 2680 AN: 1460064 Hom.: 2 Cov.: 76 AF XY: 0.00182 AC XY: 1319 AN XY: 726290

African (AFR) AF: 0.000209 AC: 7 AN: 33476

American (AMR) AF: 0.000984 AC: 44 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86236

European-Finnish (FIN) AF: 0.000844 AC: 44 AN: 52102

Middle Eastern (MID) AF: 0.000520 AC: 3 AN: 5766

European-Non Finnish (NFE) AF: 0.00226 AC: 2517 AN: 1111626

Other (OTH) AF: 0.00108 AC: 65 AN: 60342

GnomAD4 genome AF: 0.000919 AC: 140 AN: 152364 Hom.: 0 Cov.: 34 AF XY: 0.000846 AC XY: 63 AN XY: 74506

African (AFR) AF: 0.000361 AC: 15 AN: 41578

American (AMR) AF: 0.000784 AC: 12 AN: 15312

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: 4834

European-Finnish (FIN) AF: 0.000847 AC: 9 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00147 AC: 100 AN: 68036

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00122 Hom.: 0

Bravo AF: 0.000933

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00125

EpiControl AF: 0.00154

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	7.1
DANN	Benign	0.48
PhyloP100		1.6
Mutation Taster		=99/1	polymorphism

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: rs375615704; hg19: chr2-239049624;